8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions

ABSTRACT

The present invention relates to substituted xanthines of general formula 
     
       
         
         
             
             
         
       
     
     wherein R 1  to R 3  are defined as in claims  1  to  16 , the tautomers, the stereoisomers, the mixtures, the prodrugs thereof and the salts thereof which have valuable pharmacological properties, particularly an inhibiting effect on the activity of the enzyme dipeptidylpeptidase-IV (DPP-IV).

APPLICATION DATA

This application is a continuation of Ser. No. 10/639,036, filed Aug.12, 2003. This application claims benefit to U.S. provisionalapplication Ser. Nos. 60/409,312 filed Sep. 9, 2002, and 60/461,752filed Apr. 10, 2003, and German application nos. DE 102 38 243.3 filedAug. 21, 2002, and DE 103 12 353.9 filed Mar. 20, 2003.

FIELD OF INVENTION

The present invention relates to compounds having valuablepharmacological properties, particularly an inhibiting effect on theactivity of the enzyme dipeptidylpeptidase-IV (DPP-IV).

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to new substituted xanthines of generalformula

the tautomers, the stereoisomers, the mixtures, the prodrugs thereof andthe salts thereof, particularly the physiologically acceptable saltsthereof with inorganic or organic acids or bases which have valuablepharmacological properties, particularly an inhibiting effect on theactivity of the enzyme dipeptidylpeptidase-IV (DPP-IV), the preparationthereof, the use thereof for the prevention or treatment of diseases orconditions associated with an increased DPP-IV activity or capable ofbeing prevented or alleviated by reducing the DPP-IV activity,particularly type I or type II diabetes mellitus, the pharmaceuticalcompositions containing a compound of general formula (I) or aphysiologically acceptable salt thereof as well as processes for thepreparation thereof.

In the above formula I

R¹ denotes a methyl group,a methyl group which is substituted by a dimethylaminocarbonyl,pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl, tert.-butylcarbonyl ora cyclohexylcarbonyl-group,a methyl group which is substituted by a naphthyl, methylnaphthyl,methoxynaphthyl, nitronaphthyl or dimethylaminonaphthyl group,a methyl group which is substituted by a 2-phenylethenyl or a biphenylylgroup,a methyl group which is substituted by a phenyloxadiazolyl,5-methyl-3-phenyl-isoxazolyl, phenylpyridinyl, indolyl, benzothiophenyl,quinolinyl, isoquinolinyl, methylisoquinolinyl,(methoxycarbonylmethylamino)-isoquinolinyl, cinnolinyl, quinazolinyl,methylquinazolinyl, 1,2-dihydro-1-methyl-2-oxo-quinolinyl,1,2-dihydro-2-methyl-1-oxo-isoquinolinyl,3,4-dihydro-4-oxo-phthalazinyl, 3,4-dihydro-3-methyl-4-oxo-phthalazinyl,3,4-dihydro-4-oxo-quinazolinyl, 3,4-dihydro-3-methyl-4-oxo-quinazolinylor a 2-oxo-2H-chromenyl group,a 2-methoxyethyl, 2-phenyloxyethyl or 2-cyanoethyl group,a phenylcarbonylmethyl or a 1-(phenylcarbonyl)-ethyl group,a phenylcarbonylmethyl group wherein the phenyl moiety is substituted byan amino, cyanomethylamino, methylcarbonylamino, ethylcarbonylamino,isopropylcarbonylamino, methoxycarbonylamino,(ethyloxycarbonylamino)-carbonylamino or a 2-oxo-imidazolidin-1-ylgroup,a phenylcarbonylmethyl group wherein the phenyl moiety is substituted bya carboxy, methoxycarbonyl, ethyloxycarbonyl, aminocarbonyl,methylaminocarbonyl, dimethyl-aminocarbonyl or morpholin-4-ylcarbonylgroup,a phenylcarbonylmethyl group wherein the phenyl moiety is substituted bya methylsulphanyl, methylsulphinyl or methylsulphonyl group,a phenylcarbonylmethyl group wherein the phenyl moiety is substituted bya carboxymethoxy, ethyloxycarbonylmethoxy, isopropyloxycarbonylmethoxy,aminocarbonylmethoxy, methylaminocarbonylmethoxy,ethylaminocarbonylmethoxy, isopropylaminocarbonylmethoxy,dimethylaminocarbonylmethoxy, pyrrolidin-1-ylcarbonylmethoxy ormorpholin-4-ylcarbonylmethoxy group,a phenylcarbonylmethyl group wherein the phenyl moiety is substituted bya 1-(methoxy-carbonyl)-ethyloxy or a 1-(aminocarbonyl)-ethyloxy group,a phenylcarbonylmethyl group wherein the phenyl moiety is substituted bya methylsulphinylmethoxy group,a phenylcarbonylmethyl group wherein the phenyl moiety is substituted bytwo methoxy groups, ora phenylcarbonylmethyl group wherein in the phenyl moiety two adjacenthydrogen atoms are replaced by a —O—CH₂—O, —O—CH₂—CH₂—O or a—N(CH₃)—CO—O group,R² denotes a hydrogen atom,a methyl, isopropyl, 2-propen-1-yl, 2-propyn-1-yl, or phenyl group ora cyanomethyl or methoxycarbonylmethyl group andR³ denotes a 2-cyanobenzyl or 2,6-dicyanobenzyl group,a 2-methyl-2-propen-1-yl, 2-chloro-2-propen-1-yl or3-bromo-2-propen-1-yl groupa 2-buten-1-yl, 3-methyl-2-buten-1-yl or 2,3-dimethyl-2-buten-1-ylgroup,a 2-butyn-1-yl group,a 1-cyclopenten-1-ylmethyl group ora 2-furanylmethyl group.

The carboxy groups mentioned in the definition of the above mentionedgroups may be replaced by a group which can be converted into a carboxygroup in vivo or by a group which is negatively charged underphysiological conditions,

and furthermore the amino and imino groups mentioned in the definitionof the above mentioned groups may be substituted by a group which can becleaved in vivo. Such groups are described for example in WO 98/46576and by N. M. Nielsen et al. in International Journal of Pharmaceutics39, 75-85 (1987).

Compounds which contain a group that can be cleaved in vivo are prodrugsof the corresponding compounds wherein this group that can be cleaved invivo has been cleaved.

By a group which can be converted in vivo into a carboxy group is meant,for example, a hydroxymethyl group, a carboxy group esterified with analcohol wherein the alcohol moiety is preferably a C₁₋₆-alkanol, aphenyl-C₁₋₃-alkanol, a C₃₋₉-cycloalkanol, while a C₅₋₈-cycloalkanol mayadditionally be substituted by one or two C₁₋₃-alkyl groups, aC₅₋₈-cycloalkanol wherein a methylene group in the 3 or 4 position isreplaced by an oxygen atom or by an imino group optionally substitutedby a C₁₋₃-alkyl, phenyl-C₁₋₃-alkyl, phenyl-C₁₋₃-alkyloxycarbonyl orC₂₋₆-alkanoyl group and the cycloalkanol moiety may additionally besubstituted by one or two C₁₋₃-alkyl groups, a C₄₋₇-cycloalkenol, aC₃₋₅-alkenol, a phenyl-C₃₋₅-alkenol, a C₃₋₅-alkynol orphenyl-C₃₋₅-alkynol with the proviso that no bonds to the oxygen atomstart from a carbon atom which carries a double or triple bond, aC₃₋₈-cycloalkyl-C₁₋₃-alkanol, a bicycloalkanol with a total of 8 to 10carbon atoms which may additionally be substituted in the bicycloalkylmoiety by one or two C₁₋₃-alkyl groups, a1,3-dihydro-3-oxo-1-isobenzofuranol or an alcohol of formula

R_(p)—CO—O—(R_(q)CR_(r))—OH,

wherein

-   -   R_(p) denotes a C₁₋₈-alkyl, C₅₋₇-cycloalkyl, C₁₋₈-alkyloxy,        C₅₋₇-cycloalkyloxy, phenyl or phenyl-C₁₋₃-alkyl group,    -   R_(q) denotes a hydrogen atom, a C₁₋₃-alkyl, C₅₋₇-cycloalkyl or        phenyl group and    -   R_(r) denotes a hydrogen atom or a C₁₋₃-alkyl group,        by a group which is negatively charged under physiological        conditions is meant, for example, a tetrazol-5-yl,        phenylcarbonylaminocarbonyl,        trifluoromethylcarbonylaminocarbonyl, C₁₋₆-alkylsulphonylamino,        phenylsulphonylamino, benzylsulphonylamino,        trifluoromethyl-sulphonylamino,        C₁₋₆-alkylsulphonylaminocarbonyl, phenylsulphonylaminocarbonyl,        benzylsulphonylaminocarbonyl or        perfluoro-C₁₋₆-alkylsulphonylaminocarbonyl group        and by a group which can be cleaved in vivo from an imino or        amino group is meant, for example, a hydroxy group, an acyl        group such as a phenylcarbonyl group optionally mono- or        disubstituted by fluorine, chlorine, bromine or iodine atoms, by        C₁₋₃-alkyl or C₁₋₃-alkoxy groups, while the substituents may be        identical or different, a pyridinoyl group or a C₁₋₁₆-alkanoyl        group such as the formyl, acetyl, propionyl, butanoyl, pentanoyl        or hexanoyl group, a 3,3,3-trichloropropionyl or        allyloxycarbonyl group, a C₁₋₁₆-alkoxycarbonyl or        C₁₋₁₆-alkylcarbonyloxy group, wherein hydrogen atoms may be        wholly or partially replaced by fluorine or chlorine atoms such        as the methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl,        isopropoxycarbonyl, butoxycarbonyl, tert.butoxycarbonyl,        pentoxycarbonyl, hexoxycarbonyl, octyloxycarbonyl,        nonyloxycarbonyl, decyloxycarbonyl, undecyloxycarbonyl,        dodecyloxycarbonyl, hexadecyloxycarbonyl, methylcarbonyloxy,        ethylcarbonyloxy, 2,2,2-trichloroethylcarbonyloxy,        propylcarbonyloxy, isopropylcarbonyloxy, butylcarbonyloxy,        tert.butylcarbonyloxy, pentylcarbonyloxy, hexylcarbonyloxy,        octylcarbonyloxy, nonylcarbonyloxy, decylcarbonyloxy,        undecylcarbonyloxy, dodecylcarbonyloxy or hexadecylcarbonyloxy        group, a phenyl-C₁₋₆-alkoxycarbonyl group such as the        benzyloxycarbonyl, phenylethoxycarbonyl or phenylpropoxycarbonyl        group, a 3-amino-propionyl group wherein the amino group may be        mono- or disubstituted by C₁₋₆-alkyl or C₃₋₇-cycloalkyl groups        and the substituents may be identical or different, a        C₁₋₃-alkylsulphonyl-C₂₋₄-alkoxycarbonyl,        C₁₋₃-alkoxy-C₂₋₄-alkoxy-C₂₋₄-alkoxycarbonyl,        R_(p)—CO—O—(R_(q)CR_(r))—O—CO,        C₁₋₆-alkyl-CO—NH—(R_(s)CR_(t))—O—CO— or        C₁₋₆-alkyl-CO—O—(R_(s)CR_(t))—(R_(s)CR_(t))—O—CO— group, wherein        R_(p) to R_(r) are as hereinbefore defined,    -   R_(s) and R_(t), which may be identical or different, denote        hydrogen atoms or C₁₋₃-alkyl groups.

A first object of the invention relates to compounds of general formula(I) wherein

R¹ denotes a methyl group which is substituted by adimethylaminocarbonyl, pyrrolidin-1-yl-carbonyl, piperidin-1-ylcarbonyl,tert.-butylcarbonyl or a cyclohexylcarbonyl group,a methyl group which is substituted by a naphthyl, methylnaphthyl,methoxynaphthyl, nitronaphthyl or (dimethylamino)-naphthyl group,a methyl group which is substituted by a 2-phenylethenyl or a biphenylylgroup,a methyl group which is substituted by a phenyl-oxadiazolyl,5-methyl-3-phenyl-isoxazolyl, phenyl-pyridinyl, indolyl,benzothiophenyl, quinolinyl, isoquinolinyl, methylisoquinolinyl,(methoxycarbonylmethylamino)-isoquinolinyl, cinnolinyl, quinazolinyl,methylquinazolinyl, 1,2-dihydro-1-methyl-2-oxo-quinolinyl,1,2-dihydro-2-methyl-1-oxo-isoquinolinyl,3,4-dihydro-4-oxo-phthalazinyl, 3,4-dihydro-3-methyl-4-oxo-phthalazinyl,3,4-dihydro-4-oxo-quinazolinyl, 3,4-dihydro-3-methyl-4-oxo-quinazolinylor a 2-oxo-2H-chromenyl group,a 2-methoxyethyl, 2-phenyloxyethyl or 2-cyanoethyl group,a phenylcarbonylmethyl or a 1-(phenylcarbonyl)-ethyl group,a phenylcarbonylmethyl group wherein the phenyl moiety is substituted byan amino, cyanomethylamino, methylcarbonylamino, ethylcarbonylamino,isopropylcarbonylamino, methoxycarbonylamino,(ethyloxycarbonylamino)-carbonylamino or a 2-oxo-imidazolidin-1-ylgroup,a phenylcarbonylmethyl group wherein the phenyl moiety is substituted bya carboxy, methoxycarbonyl, ethyloxycarbonyl, aminocarbonyl,methylaminocarbonyl, dimethyl-aminocarbonyl or morpholin-4-ylcarbonylgroup,a phenylcarbonylmethyl group wherein the phenyl moiety is substituted bya methylsulphanyl, methylsulphinyl or methylsulphonyl group,a phenylcarbonylmethyl group wherein the phenyl moiety is substituted bya carboxymethoxy, ethyloxycarbonylmethoxy, isopropyloxycarbonylmethoxy,aminocarbonylmethoxy, methylaminocarbonylmethoxy,ethylaminocarbonylmethoxy, isopropylaminocarbonylmethoxy,dimethylaminocarbonylmethoxy, pyrrolidin-1-ylcarbonylmethoxy ormorpholin-4-ylcarbonylmethoxy group,a phenylcarbonylmethyl group wherein the phenyl moiety is substituted bya 1-(methoxy-carbonyl)-ethyloxy or a 1-(aminocarbonyl)-ethyloxy group,a phenylcarbonylmethyl group wherein the phenyl moiety is substituted bya methylsulphinylmethoxy group,a phenylcarbonylmethyl group wherein the phenyl moiety is substituted bytwo methoxy groups ora phenylcarbonylmethyl group wherein in the phenyl moiety two adjacenthydrogen atoms are replaced by a —O—CH₂—O, —O—CH₂—CH₂—O or a—N(CH₃)—CO—O group,R² denotes a methyl, isopropyl or phenyl groupandR³ denotes a 2-methyl-2-propen-1-yl, 2-chloro-2-propen-1-yl or3-bromo-2-propen-1-yl groupa 2-buten-1-yl or 2,3-dimethyl-2-buten-1-yl group,a 2-butyn-1-yl group,a 1-cyclopenten-1-ylmethyl group ora 2-furanylmethyl group,as well as the compounds

-   1-(2-cyano-ethyl)-3-methyl-7-(2-cyano-benzyl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-(2-{2-[(ethoxycarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-(2-{2-[(aminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-(2-{3-[(methanesulphinyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-(1-methyl-2-oxo-2-phenyl-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-(2-phenoxy-ethyl)-3-methyl-7-(2-cyano-benzyl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-(2-phenyl-2-oxo-ethyl)-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-(2-{3-[(ethoxycarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-(2-{2-[(methylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-(2-{2-[(dimethylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-(2-methoxy-ethyl)-3-methyl-7-(2-cyano-benzyl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-methyl-3-[(methoxycarbonyl)methyl]-7-(2-cyano-benzyl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-methyl-3-cyanomethyl-7-(2-cyano-benzyl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-methyl-3-(2-propyn-1-yl)-7-(2-cyano-benzyl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-{2-[3-(2-oxo-imidazolidin-1-yl)-phenyl]-2-oxo-ethyl}-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-methyl-3-(2-propen-1-yl)-7-(2-cyano-benzyl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-(2-{2-[(ethylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-methyl-3-phenyl-7-(2-cyano-benzyl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-[2-(2-amino-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,-   1-(2-phenyl-2-oxo-ethyl)-3-cyanomethyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-[(quinolin-2-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-[(2-oxo-2H-chromen-4-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-[(cinnolin-4-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-[(1-methyl-2-oxo-1,2-dihydro-quinolin-4-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-[(4-oxo-3,4-dihydro-phthalazin-1-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-[(quinazolin-4-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-[(5-methyl-3-phenyl-isoxazol-4-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-[(isoquinolin-3-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-[(3-phenyl-[1,2,4]oxadiazol-5-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-[(4-phenyl-pyridin-2-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-[(5-phenyl-pyridin-2-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-[(3-methyl-4-oxo-3,4-dihydro-phthalazin-1-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-[2-(3-methylsulphanyl-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-[2-(3-methanesulphinyl-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-[2-(3-methanesulphonyl-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-[2-(3-carboxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-[2-(3-methoxycarbonyl-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-{2-[3-(methylaminocarbonyl)-phenyl]-2-oxo-ethyl}-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-{2-[3-(dimethylaminocarbonyl)-phenyl]-2-oxo-ethyl}-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-{2-[3-(morpholin-4-yl-carbonyl)-phenyl]-2-oxo-ethyl}-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-[2-(2-carboxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-[2-(2-ethoxycarbonyl-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-{2-[2-(dimethylaminocarbonyl)-phenyl]-2-oxo-ethyl}-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-{2-[2-(morpholin-4-yl-carbonyl)-phenyl]-2-oxo-ethyl}-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-[2-(2,6-dimethoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-((E)-3-phenyl-allyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-[(benzo[b]thiophen-3-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-[(1H-indol-3-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-[(biphenyl-4-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-(2-cyclohexyl-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-(3,3-dimethyl-2-oxo-butyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-({5-[(methoxycarbonyl)methylamino]-isoquinolin-1-yl}methyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-(2-dimethylamino-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-[2-(piperidin-1-yl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-[(2-methyl-1-oxo-1,2-dihydro-isoquinolin-4-yl)methyl]-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-[2-(2,3-dimethoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-[2-(pyrrolidin-1-yl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-[2-(2,3-dihydro-benzo[1,4]dioxin-5-yl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-[2-(3-methyl-2-oxo-2,3-dihydro-benzooxazol-7-yl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-[2-(benzo[1,3]dioxol-4-yl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-methyl-3-isopropyl-7-(2-cyano-benzyl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-[2-(2-cyanomethylamino-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-[(isoquinolin-1-yl)methyl]-3-[(methoxycarbonyl)methyl]-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-(2-{2-[(isopropyloxycarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-[2-(2-{[(ethoxycarbonylamino)carbonyl]amino}-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-[2-(2-acetylamino-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,-   1-(2-{2-[(methylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,-   1-methyl-7-(2-cyano-benzyl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-(2-{2-[(isopropylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-(2-{2-[(methoxycarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-[2-(3-methyl-2-oxo-2,3-dihydro-benzooxazol-4-yl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-[2-(2-nitro-3-methoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-[2-(2-amino-3-methoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-[2-(2-oxo-2,3-dihydro-benzooxazol-7-yl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(3-methyl-1-buten-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,-   1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-cyano-benzyl)-8-(3-amino-piperidin-1-yl)-xanthine,-   1-[2-(3-carboxymethoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine    and-   1-[2-(2-carboxymethoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,    the tautomers, enantiomers, diastereomers, the mixtures thereof, the    prodrugs thereof and the salts thereof.

A first preferred sub-group of the first object of the inventioncomprises compounds of general formula I wherein

R¹ denotes a 4-methoxy-1-naphthylmethyl group,a 2-quinolinylmethyl, 4-quinolinylmethyl or a 6-quinolinylmethyl group,a 1-isoquinolinylmethyl, 3-methyl-1-isoquinolinylmethyl,4-methyl-1-isoquinolinylmethyl ora 3-isoquinolinylmethyl group ora 2-quinazolinylmethyl, 4-methyl-2-quinazolinylmethyl or a4-quinazolinylmethyl group,R² denotes a methyl group andR³ denotes a 2-buten-1-yl or a 2-butyn-1-yl group,the tautomers, enantiomers, diastereomers, the mixtures thereof and thesalts thereof.

A second preferred sub-group of the first object of the inventioncomprises compounds of general formula I, wherein

R¹ denotes a [2-(methylcarbonylamino)-phenyl]-carbonylmethyl group,a [2-(ethylcarbonylamino)-phenyl]-carbonylmethyl group ora [2-(isopropylcarbonylamino)-phenyl]-carbonylmethyl group,R² denotes a methyl group andR³ denotes a 2-buten-1-yl or a 2-butyn-1-yl group,the tautomers, enantiomers, diastereomers, the mixtures thereof and thesalts thereof.

A third preferred sub-group of the first object of the inventioncomprises compounds of general formula I according to claim 1, wherein

R¹ denotes a [2-(aminocarbonylmethoxy)-phenyl]-carbonylmethyl group,[2-(methylaminocarbonylmethoxy)-phenyl]-carbonylmethyl group,a [2-(ethylaminocarbonylmethoxy)-phenyl]-carbonylmethyl group ora [2-(isopropylaminocarbonylmethoxy)-phenyl]-carbonylmethyl group,R² denotes a methyl group andR³ denotes a 2-buten-1-yl group,a 2-butyn-1-yl group ora 1-cyclopenten-1-ylmethyl group,the tautomers, enantiomers, diastereomers, the mixtures thereof and thesalts thereof.

A second object of the invention relates to compounds of general formulaI, wherein

R¹ denotes a methyl group which is substituted by a naphthyl,fluoronaphthyl, methylnaphthyl, methoxynaphthyl,(difluoromethoxy)-naphthyl, cyanonaphthyl, nitronaphthyl or(dimethylamino)-naphthyl group,a methyl group which is substituted by a phenanthrenyl group,a methyl group which is substituted by a 2-phenylethenyl,2-[(trifluoromethyl)-phenyl]-ethenyl, 2-(nitrophenyl)ethenyl,2-(pentafluorophenyl)ethenyl or a biphenylyl group,a methyl group which is substituted by a phenyloxadiazolyl,phenylpyridinyl, indolyl, methylindolyl,dimethyl-6,7-dihydro-5H-[2]pyrindinyl, benzimidazolyl,methylbenzimidazolyl, (cyanoethyl)-benzimidazolyl,(methylaminocarbonylmethyl)benzimidazolyl, benzylbenzimidazolyl,benzofuranyl, acetylbenzofuranyl, cyanobenzofuranyl, benzoxazolyl,nitrobenzoxazolyl, benzothiophenyl, methylbenzothiazolyl, quinolinyl,methoxyquinolinyl, isoquinolinyl, methylisoquinolinyl,(difluoromethyl)-isoquinolinyl, (trifluoromethyl)-isoquinolinyl,dimethylisoquinolinyl, (1-cyano-1-methyl-ethyl)isoquinolinyl,phenyl-isoquinolinyl, methoxyisoquinolinyl,methoxy-chloro-isoquinolinyl, methoxy-bromo-isoquinolinyl,(methoxycarbonylmethylamino)-isoquinolinyl,dimethyl-5,6,7,8-tetrahydroisoquinolinyl,1,2,3,4-tetrahydrophenanthridinyl, cinnolinyl, quinazolinyl,methylquinazolinyl, isopropylquinazolinyl, cyclopropylquinazolinyl,phenylquinazolinyl, aminoquinazolinyl, (dimethylamino)-quinazolinyl,pyrrolidin-1-ylquinazolinyl, piperidin-1-ylquinazolinyl,piperazin-1-ylquinazolinyl, morpholin-4-ylquinazolinyl,ethoxyquinazolinyl, isopropyloxyquinazolinyl, phenyloxyquinazolinyl,imidazo[1,2-a]pyridinyl, methyl-imidazo[1,2-a]pyridinyl,phenylimidazo[1,2-a]pyridinyl, benzylimidazo[1,2-a]pyridinyl,pyrazolo[1,5-a]pyridinyl, quinoxalinyl, methylquinoxalinyl,dimethylquinoxalinyl, trimethylquinoxalinyl, phenylquinoxalinyl,methylphthalazinyl, naphthyridinyl, 2,3-dihydro-benzo[1,4]dioxinyl,1,2-dihydro-2-oxo-quinolinyl, 1,2-dihydro-1-methyl-2-oxo-quinolinyl,1,2-dihydro-2-methyl-1-oxo-isoquinolinyl,3,4-dihydro-4-oxo-phthalazinyl, 3,4-dihydro-3-methyl-4-oxo-phthalazinyl,3,4-dihydro-4-oxo-quinazolinyl, 3,4-dihydro-3-methyl-4-oxo-quinazolinylor a 2-oxo-2H-chromenyl group,a phenylcarbonylmethyl group,a phenylcarbonylmethyl group wherein the phenyl moiety is substituted byan amino, cyanomethylamino, (ethyloxycarbonylmethyl)amino,(methylaminocarbonyl)methylamino, methylcarbonylamino,ethylcarbonylamino, isopropylcarbonylamino, phenylcarbonylamino,methoxycarbonylamino, (ethyloxycarbonylamino)-carbonylamino or a2-oxo-imidazolidin-1-yl group,a phenylcarbonylmethyl group wherein the phenyl moiety is substituted bya phenyl group,a phenylcarbonylmethyl group wherein the phenyl moiety is substituted bya carboxy, methoxycarbonyl, ethyloxycarbonyl, aminocarbonyl,methylaminocarbonyl, dimethyl-aminocarbonyl or morpholin-4-ylcarbonylgroup,a phenylcarbonylmethyl group wherein the phenyl moiety is substituted bya methylsulphanyl, methylsulphinyl or methylsulphonyl group,a phenylcarbonylmethyl group wherein the phenyl moiety is substituted bya methoxy, difluoromethoxy, trifluoromethoxy, ethyloxy, isopropyloxy orphenyloxy group,a phenylcarbonylmethyl group wherein the phenyl moiety is substituted bya methylsulphinylmethoxy, carboxymethoxy, ethyloxycarbonylmethoxy,isopropyloxycarbonylmethoxy, aminocarbonylmethoxy,methylaminocarbonylmethoxy, ethylaminocarbonylmethoxy,isopropylaminocarbonylmethoxy, dimethylaminocarbonylmethoxy,pyrrolidin-1-ylcarbonylmethoxy or morpholin-4-ylcarbonylmethoxy group,a phenylcarbonylmethyl group wherein the phenyl moiety is substituted bya 1-(ethyloxycarbonyl)-1-methyl-ethyloxy, 1-(methoxycarbonyl)-ethyloxyor a 1-(aminocarbonyl)-ethyloxy group,a phenylcarbonylmethyl group wherein the phenyl moiety is substituted bytwo methoxy groups,a phenylcarbonylmethyl group wherein the phenyl moiety is substituted bya methoxy group and a nitro group,a phenylcarbonylmethyl group wherein the phenyl moiety is substituted bya methoxy group and an amino group,a phenylcarbonylmethyl group wherein in the phenyl moiety two adjacenthydrogen atoms are replaced by a —O—CH₂—O, —O—CF₂—O, —O—CH₂—CH₂—O,—NH—CO—NH, —N(CH₃)—CO—NH, —N(CH₃)—CO—N(CH₃), —NH—CO—O— or a —N(CH₃)—CO—Ogroup,a (2-phenylethyl)carbonylmethyl group,a naphthylcarbonylmethyl, indolylcarbonylmethyl orquinolinylcarbonylmethyl group ora 2-cyanimino-2-phenyl-ethyl group,R² denotes a methyl, isopropyl, cyclopropyl, phenyl or fluorophenylgroup andR³ denotes a 2-methyl-2-propen-1-yl, 2-chloro-2-propen-1-yl or3-bromo-2-propen-1-yl groupa 1-buten-1-yl, 3-methyl-1-buten-1-yl, 2-buten-1-yl,2-methyl-2-buten-1-yl- or 2,3-dimethyl-2-buten-1-yl group,a 2-butyn-1-yl group,a 1-cyclopenten-1-ylmethyl group ora 2-furanylmethyl group,the tautomers, enantiomers, diastereomers, the mixtures thereof, theprodrugs thereof and the salts thereof.

A preferred sub-group of the second object of the invention comprisescompounds of general formula I wherein

R¹ and R² are as hereinbefore defined andR³ denotes a 1-buten-1-yl, 2-buten-1-yl or 2-butyn-1-yl group,the tautomers, enantiomers, diastereomers, the mixtures thereof and thesalts thereof.

A particularly preferred sub-group of the second object of the inventioncomprises compounds of general formula I wherein

R¹ denotes a methyl group which is substituted by a naphthyl,fluoronaphthyl, methylnaphthyl, methoxynaphthyl,(difluoromethoxy)-naphthyl, cyanonaphthyl or nitronaphthyl group,a methyl group which is substituted by a 2-(pentafluorophenyl)ethenylgroup,a methyl group which is substituted by a benzofuranyl,methylbenzothiazolyl, quinolinyl, methoxyquinolinyl, isoquinolinyl,methylisoquinolinyl, (difluoromethyl)-isoquinolinyl,(trifluoromethyl)-isoquinolinyl, dimethylisoquinolinyl,(1-cyano-1-methyl-ethyl)isoquinolinyl, phenylisoquinolinyl,methoxyisoquinolinyl, 1,2,3,4-tetrahydrophenanthridinyl, quinazolinyl,methylquinazolinyl, isopropylquinazolinyl, cyclopropylquinazolinyl,phenylquinazolinyl, aminoquinazolinyl, (dimethylamino)-quinazolinyl,pyrrolidin-1-ylquinazolinyl, piperidin-1-ylquinazolinyl,piperazin-1-ylquinazolinyl, morpholin-4-ylquinazolinyl,ethoxyquinazolinyl, isopropyloxyquinazolinyl, quinoxalinyl,methyl-quinoxalinyl, dimethylquinoxalinyl, trimethylquinoxalinyl,phenylquinoxalinyl, [1,5]naphthyridinyl, [1,6]naphthyridinyl,[1,8]naphthyridinyl or a 1,2-dihydro-1-methyl-2-oxo-quinolinyl group,a phenylcarbonylmethyl group,a phenylcarbonylmethyl group wherein the phenyl moiety is substituted bya phenyl group,a phenylcarbonylmethyl group wherein the phenyl moiety is substituted bya methoxy, difluoromethoxy, trifluoromethoxy, ethyloxy, isopropyloxy orphenyloxy group,a phenylcarbonylmethyl group wherein in the phenyl moiety two adjacenthydrogen atoms are replaced by a —O—CH₂—O, —O—CF₂—O, —O—CH₂—CH₂—O,—N(CH₃)—CO—N(CH₃) or a —N(CH₃)—CO—O group,a naphthylcarbonylmethyl, indolylcarbonylmethyl orquinolinylcarbonylmethyl group ora 2-cyanimino-2-phenyl-ethyl group,R² denotes a methyl, isopropyl, cyclopropyl, phenyl or 4-fluorophenylgroup andR³ denotes a 1-buten-1-yl, 2-buten-1-yl or a 2-butyn-1-yl group,the tautomers, enantiomers, diastereomers, the mixtures thereof and thesalts thereof.

A second preferred sub-group of the second object of the inventioncomprises compounds of general formula I, wherein R¹ and R² are definedas immediately above and R³ denotes a 1-buten-1-yl group,

the tautomers, enantiomers, diastereomers, the mixtures thereof and thesalts thereof.

A third preferred sub-group of the second object of the inventioncomprises compounds of general formula I wherein R¹ and R² are definedas immediately above and R³ denotes a 2-buten-1-yl group,

the tautomers, enantiomers, diastereomers, the mixtures thereof and thesalts thereof.

A fourth preferred sub-group of the second object of the inventioncomprises compounds of general formula I wherein R¹ and R² are definedas immediately above and R³ denotes a 2-butyn-1-yl group,

the tautomers, enantiomers, diastereomers, the mixtures thereof and thesalts thereof.

A third object of the invention relates to compounds of general formulaI wherein

R¹ denotes a methyl group which is substituted by a naphthyl,fluoronaphthyl, methylnaphthyl, methoxynaphthyl,(difluoromethoxy)-naphthyl, cyanonaphthyl or nitronaphthyl-group,a methyl group which is substituted by a 2-(pentafluorophenyl)ethenylgroup, ora methyl group which is substituted by a benzofuranyl,methylbenzothiazolyl, quinolinyl, methoxyquinolinyl, isoquinolinyl,methylisoquinolinyl, (difluoromethyl)-isoquinolinyl,(trifluoromethyl)-isoquinolinyl, dimethylisoquinolinyl,(1-cyano-1-methyl-ethyl)-isoquinolinyl, phenylisoquinolinyl,methoxyisoquinolinyl, 1,2,3,4-tetrahydrophenanthridinyl, quinazolinyl,methylquinazolinyl, isopropylquinazolinyl, cyclopropylquinazolinyl,phenylquinazolinyl, aminoquinazolinyl, (dimethylamino)-quinazolinyl,pyrrolidin-1-ylquinazolinyl, piperidin-1-ylquinazolinyl,piperazin-1-ylquinazolinyl, morpholin-4-ylquinazolinyl,ethoxyquinazolinyl, isopropyloxyquinazolinyl, quinoxalinyl,methylquinoxalinyl, dimethylquinoxalinyl, trimethylquinoxalinyl,phenylquinoxalinyl, [1,5]naphthyridinyl, [1,6]naphthyridinyl,[1,8]naphthyridinyl or a 1,2-dihydro-1-methyl-2-oxo-quinolinyl group,R² denotes a methyl, isopropyl, cyclopropyl or phenyl group andR³ denotes a 2-chlorobenzyl, 2-bromobenzyl, 2-ethynylbenzyl or2-cyanobenzyl group,the tautomers, enantiomers, diastereomers, the mixtures thereof and thesalts thereof.

A first preferred sub-group of the third object of the inventioncomprises compounds of general formula I wherein

R¹ denotes a (3-methyl-isoquinolin-1-yl)methyl group,R² denotes a methyl group andR³ denotes a 2-chlorobenzyl, 2-bromobenzyl, 2-ethynylbenzyl or2-cyanobenzyl group,the tautomers, enantiomers, diastereomers, the mixtures thereof and thesalts thereof.

A second preferred sub-group of the third object of the inventioncomprises compounds of general formula I wherein R¹ and R² are ashereinbefore defined and R³ denotes a 2-chlorobenzyl group, thetautomers, enantiomers, diastereomers, the mixtures thereof and thesalts thereof.

A third preferred sub-group of the third object of the inventioncomprises compounds of general formula I wherein R¹ and R² are ashereinbefore defined and R³ denotes a 2-bromobenzyl group, thetautomers, enantiomers, diastereomers, the mixtures thereof and thesalts thereof.

A fourth preferred sub-group of the third object of the inventioncomprises compounds of general formula I wherein R¹ and R² are ashereinbefore defined and R³ denotes a 2-ethynylbenzyl group, thetautomers, enantiomers, diastereomers, the mixtures thereof and thesalts thereof.

A fifth preferred sub-group of the third object of the inventioncomprises compounds of general formula I wherein R¹ and R² are ashereinbefore defined and R³ denotes a 2-cyanobenzyl group, thetautomers, enantiomers, diastereomers, the mixtures thereof and thesalts thereof.

Most particularly preferred are the following compounds of generalformula I:

-   (1)    1-[(quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,-   (2)    1-(2-{2-[(ethylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,-   (3)    1-(2-{2-[(methylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,-   (4)    1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,-   (5)    1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,-   (6)    1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,-   (7)    1-[(4-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,-   (8)    1-[(4-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,-   (9)    1-[2-(2,3-dihydro-benzo[1,4]dioxin-5-yl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine,-   (10)    1-[(4-methoxy-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,-   (11)    1-[(4-methoxy-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,-   (12)    1-[2-(benzo[1,3]dioxol-4-yl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,-   (13)    1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine,-   (14)    1-(2-{2-[(isopropylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,-   (15)    1-(2-{2-[(methylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,-   (16)    1-(2-{2-[(methylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,-   (17)    1-(2-{2-[(isopropylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,-   (18)    1-(2-{2-[(isopropylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,-   (19)    1-[(4-cyano-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,-   (20)    1-[(4-phenyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,-   (21)    1-[(8-methyl-quinoxalin-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,-   (22)    1-[(4-fluoro-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,-   (23)    1-((E)-3-pentafluorophenyl-allyl)-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,-   (24)    1-[(3-trifluoromethyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,-   (25)    1-[(3-difluoromethyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,-   (26)    1-[2-(biphenyl-2-yl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,-   (27)    1-[(3-methyl-isoquinolin-1-yl)methyl]-3-cyclopropyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,-   (28)    1-[2-(3-methoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,-   (29)    1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-chloro-benzyl)-8-((R)-3-amino-piperidin-1-yl)-xanthine    and-   (30)    1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-bromo-benzyl)-8-((R)-3-amino-piperidin-1-yl)-xanthine    as well as the tautomers, enantiomers, diastereomers, the mixtures    thereof and the salts thereof.

According to the invention the compounds of general formula I areobtained by methods known per se, for example by the following methods:

a) reacting a compound of general formula

whereinR¹ to R³ are as hereinbefore defined andZ¹ denotes a leaving group such as a halogen atom, a substitutedhydroxy, mercapto, sulphinyl, sulphonyl or sulphonyloxy group such as achlorine or bromine atom, a methanesulphonyl or methanesulphonyloxygroup,with 3-aminopiperidine, the enantiomers thereof or the salts thereof.

The reaction is expediently carried out in a solvent such asisopropanol, butanol, tetrahydrofuran, dioxane, dimethylformamide,dimethylsulphoxide, ethyleneglycol monomethylether, ethyleneglycoldiethylether or sulpholane, optionally in the presence of an inorganicor tertiary organic base, e.g. sodium carbonate, potassium carbonate orpotassium hydroxide, a tertiary organic base, e.g. triethylamine, or inthe presence of N-ethyl-diisopropylamine (Hünig base), while theseorganic bases may simultaneously also serve as solvent, and optionallyin the presence of a reaction accelerator such as an alkali metal halideor a palladium-based catalyst at temperatures between −20 and 180° C.,but preferably at temperatures between −10 and 120° C. The reaction may,however, also be carried out without a solvent or in an excess of the3-aminopiperidine.

b) deprotecting a compound of general formula

wherein R¹, R² and R³ are as hereinbefore defined.

The tert.-butyloxycarbonyl group is preferably cleaved by treatment withan acid such as trifluoroacetic acid or hydrochloric acid or bytreatment with bromotrimethylsilane or iodotrimethylsilane, optionallyusing a solvent such as methylene chloride, ethyl acetate, dioxane,methanol, isopropanol or diethyl ether at temperatures between 0 and 80°C.

c) In order to prepare a compound of general formula I wherein R¹according to the definition provided hereinbefore contains a carboxygroup:deprotecting a compound of general formula

wherein R² and R³ are as hereinbefore defined and R^(1′) contains acarboxy group protected by a C₁₋₄-alkyl group.

The protecting group is cleaved by hydrolysis, for example, using anacid such as hydrochloric acid or sulphuric acid or an alkali metalhydroxide such as lithium hydroxide, sodium hydroxide or potassiumhydroxide in a solvent such as methanol, ethanol, isopropanol,tetrahydrofuran or dioxane in the presence of water.

In the reactions described hereinbefore, any reactive groups presentsuch as carboxy, amino, alkylamino or imino groups may be protectedduring the reaction by conventional protecting groups which are cleavedagain after the reaction.

For example, a protecting group for a carboxy group may be atrimethylsilyl, methyl, ethyl, tert.butyl, benzyl or tetrahydropyranylgroup and

protecting groups for an amino, alkylamino or imino group may be aformyl, acetyl, trifluoroacetyl, ethoxycarbonyl, tert.butoxycarbonyl,benzyloxycarbonyl, benzyl, methoxy-benzyl or 2,4-dimethoxybenzyl groupand additionally, for the amino group, a phthalyl group.

Any protecting group used is optionally subsequently cleaved for exampleby hydrolysis in an aqueous solvent, e.g. in water, isopropanol/water,acetic acid/water, tetrahydrofuran/water or dioxane/water, in thepresence of an acid such as trifluoroacetic acid, hydrochloric acid orsulphuric acid or in the presence of an alkali metal base such as sodiumhydroxide or potassium hydroxide or aprotically, e.g. in the presence ofiodotrimethylsilane, at temperatures between 0 and 120° C., preferablyat temperatures between 10 and 100° C.

However, a benzyl, methoxybenzyl or benzyloxycarbonyl group is cleaved,for example, hydrogenolytically, e.g. with hydrogen in the presence of acatalyst such as palladium/charcoal in a suitable solvent such asmethanol, ethanol, ethyl acetate or glacial acetic acid, optionally withthe addition of an acid such as hydrochloric acid at temperaturesbetween 0 and 100° C., but preferably at temperatures between 20 and 60°C., and at a hydrogen pressure of 1 to 7 bar, but preferably 3 to 5 bar.A 2,4-dimethoxybenzyl group, however, is preferably cleaved intrifluoroacetic acid in the presence of anisol.

A tert.butyl or tert.butyloxycarbonyl group is preferably cleaved bytreating with an acid such as trifluoroacetic acid or hydrochloric acidor by treating with iodotrimethylsilane, optionally using a solvent suchas methylene chloride, dioxan, methanol or diethylether.

A trifluoroacetyl group is preferably cleaved by treating with an acidsuch as hydrochloric acid, optionally in the presence of a solvent suchas acetic acid at temperatures between 50 and 120° C., or by treatingwith sodium hydroxide solution, optionally in the presence of a solventsuch as tetrahydrofuran at temperatures between 0 and 50° C.

A phthalyl group is preferably cleaved in the presence of hydrazine or aprimary amine such as methylamine, ethylamine or n-butylamine in asolvent such as methanol, ethanol, isopropanol, toluene/water or dioxanat temperatures between 20 and 50° C.

Moreover, the compounds of general formula I obtained may be resolvedinto their enantiomers and/or diastereomers, as mentioned hereinbefore.Thus, for example, cis/trans mixtures may be resolved into their cis andtrans isomers, and compounds with at least one optically active carbonatom may be separated into their enantiomers.

Thus, for example, the cis/trans mixtures may be resolved bychromatography into the cis and trans isomers thereof, the compounds ofgeneral formula I obtained which occur as racemates may be separated bymethods known per se (cf. Allinger N. L. and Eliel E. L. in “Topics inStereochemistry”, Vol. 6, Wiley Interscience, 1971) into their opticalantipodes and compounds of general formula I with at least 2 asymmetriccarbon atoms may be resolved into their diastereomers on the basis oftheir physical-chemical differences using methods known per se, e.g. bychromatography and/or fractional crystallisation, and, if thesecompounds are obtained in racemic form, they may subsequently beresolved into the enantiomers as mentioned above.

The enantiomers are preferably separated by column separation on chiralphases or by recrystallisation from an optically active solvent or byreacting with an optically active substance which forms salts orderivatives such as e.g. esters or amides with the racemic compound,particularly acids and the activated derivatives or alcohols thereof,and separating the diastereomeric mixture of salts or derivatives thusobtained, e.g. on the basis of their differences in solubility, whilstthe free antipodes may be released from the pure diastereomeric salts orderivatives by the action of suitable agents. Optically active acids incommon use are e.g. the D- and L-forms of tartaric acid ordibenzoyltartaric acid, di-o-tolyltartaric acid, malic acid, mandelicacid, camphorsulphonic acid, glutamic acid, aspartic acid or quinicacid. An optically active alcohol may be for example (+) or (−)-mentholand an optically active acyl group in amides, for example, may be a (+)-or (−)-menthyloxycarbonyl.

Furthermore, the compounds of formula I may be converted into the saltsthereof, particularly for pharmaceutical use into the physiologicallyacceptable salts with inorganic or organic acids. Acids which may beused for this purpose include for example hydrochloric acid, hydrobromicacid, sulphuric acid, phosphoric acid, fumaric acid, succinic acid,lactic acid, citric acid, tartaric acid or maleic acid.

Moreover, if the new compounds of formula I thus obtained contain acarboxy group, they may subsequently, if desired, be converted into thesalts thereof with inorganic or organic bases, particularly forpharmaceutical use into the physiologically acceptable salts thereof.Suitable bases for this purpose include for example sodium hydroxide,potassium hydroxide, arginine, cyclohexylamine, ethanolamine,diethanolamine and triethanolamine.

The compounds of general formulae II to IV used as starting materialsare either known from the literature or may be obtained by methods knownfrom the literature (cf. Examples I to LXXI).

As already mentioned hereinbefore, the compounds of general formula Iaccording to the invention and the physiologically acceptable saltsthereof have valuable pharmacological properties, particularly aninhibiting effect on the enzyme DPP-IV.

The biological properties of the new compounds were investigated asfollows:

The ability of the substances and their corresponding salts to inhibitthe DPP-IV activity can be demonstrated in a test set-up in which anextract of human colon carcinoma cell line Caco-2 is used as the DPP-IVsource. The differentiation of the cells in order to induce the DPP-IVexpression was carried out as described by Reiher et al. in an articleentitled “Increased expression of intestinal cell line Caco-2”, whichappeared in Proc. Natl. Acad. Sci. Vol. 90, pages 5757-5761 (1993). Thecell extract was obtained from cells solubilised in a buffer (10 mM TrisHCl, 0.15 M NaCl, 0.04 t.i.u. aprotinin, 0.5% Nonidet-P40, pH 8.0) bycentrifuging at 35,000 g of for 30 minutes at 4° C. (to remove celldebris).

The DPP-IV assay was carried out as follows:

50 μl substrate solution (AFC; AFC is amido-4-trifluoromethylcoumarin),final concentration 100 μM, were placed in black microtitre plates. 20μl of assay buffer (final concentrations 50 mM Tris HCl pH 7.8, 50 mMNaCl, 1% DMSO) was pipetted in. The reaction was started by adding 30 μlof solubilised Caco-2 protein (final concentration 0.14 μg of proteinper well). The test substances to be investigated were typically addedprediluted in 20 μl, and the volume of assay buffer was then reducedaccordingly. The reaction was carried out at ambient temperature,incubating for 60 minutes. Then the fluorescence was measured in aVictor 1420 Multilabel Counter, the excitation wavelength being 405 nmand the emission wavelength being 535 nm. Blank readings (correspondingto 0% activity) were obtained in mixtures without any Caco-2 protein(volume replaced by assay buffer), control values (corresponding to 100%activity) were obtained in mixtures with no substance added. The potencyof the test substances in question, expressed as IC₅₀ values, wascalculated from dosage/activity curves consisting of 11 measuring pointsin each case. The following results were obtained:

Compound DPP-IV inhibition (Example no.) IC₅₀ [nM] 2(3)  2160 2(9)  2642(12)  16 2(17)  32 2(20)  12 2(25)  4 2(27)  9 2(35)  5 2(37)  5 2(43) 6 2(51)  6 2(52)  9 2(59)  250 2(66)  22 2(80)  1 2(86)  2 2(96)  22(99)  1 2(100) 3 2(108) 3 2(129) 3 2(130) 3 2(131) 3 2(132) 1 2(135) 32(137) 13 2(138) 8 2(139) 4 2(142) 1 2(145) 4 2(148) 1 2(150) 1 2(151) 32(152) 4 2(185) 3 2(217) 4 2(247) 2 2(251) 12 2(256) 8 2(260) 13 2(264)6 2(277) 6 2(280) 5 2(285) 3 2(287) 11 2(288) 14

The compounds prepared according to the invention are well tolerated, asfor example when 10 mg/kg of the compound of Example 2(80) wereadministered to rats by oral route no changes in the animals' behaviourcould be detected.

In view of their ability to inhibit DPP-IV activity, the compounds ofgeneral formula I according to the invention and the correspondingpharmaceutically acceptable salts thereof are suitable for treating allthose conditions or illnesses which can be influenced by the inhibitionof the DPP-IV activity. It is therefore to be expected that thecompounds according to the invention will be suitable for the preventionor treatment of diseases or conditions such as type 1 and type 2diabetes mellitus, diabetic complications (such as e.g. retinopathy,nephropathy or neuropathies), metabolic acidosis or ketosis, reactivehypoglycaemia, insulin resistance, metabolic syndrome, dyslipidaemias ofvarious origins, arthritis, atherosclerosis and related diseases,obesity, allograft transplantation and calcitonin-induced osteoporosis.In addition these substances are capable of preventing B-celldegeneration such as e.g. apoptosis or necrosis of pancreatic B-cells.The substances are also suitable for improving or restoring the functionof pancreatic cells and also increasing the number and size ofpancreatic B-cells. Additionally, and on the basis of the role of theGlucagon-Like Peptides, such as e.g. GLP-1 and GLP-2 and their link withDPP-IV inhibition, it is likely that the compounds according to theinvention are suitable for achieving, inter alia, a sedative oranxiety-relieving effect and also for favourably affecting catabolicstates after operations or hormonal stress responses or reducingmortality or morbidity after myocardial infarct. They are also suitablefor treating all conditions which are connected with the above mentionedeffects and which are mediated by GLP-1 or GLP-2. The compoundsaccording to the invention may also be used as diuretics orantihypertensives and are suitable for preventing and treating acuterenal failure. Furthermore, the compounds according to the invention maybe used to treat inflammatory diseases of the respiratory tract. Theyare also suitable for the prevention and treatment of chronicinflammatory intestinal diseases such as e.g. irritable bowel syndrome(IBS), Crohn's disease or ulcerative colitis and also pancreatitis. Itis also likely that they can be used for all kinds of damage to orimpairment of the gastrointestinal tract such as colitis and enteritis,for example. It is also expected that DPP-IV inhibitors and hence alsothe compounds according to the invention may be used to treatinfertility or to improve fertility in humans or mammals, particularlywhen the infertility is connected with insulin resistance or polycysticovary syndrome. On the other hand these substances are suitable foraffecting sperm motility and can thus be used as male contraceptives.The substances are also suitable for treating deficiencies of growthhormone which are associated with reduced stature, and may also be usedto advantage in any indications in which growth hormone may be used. Thecompounds according to the invention are also suitable, on the basis oftheir inhibitory effect on DPP-IV, for treating various autoimmunediseases such as e.g. rheumatoid arthritis, multiple sclerosis,thyroiditis and Basedow's disease, etc. They may also be used to treatviral diseases and also, for example, in HIV infections, for stimulatingblood production, in benign prostatic—hyperplasia, gingivitis, as wellas for the treatment of neuronal defects and neurodegenerative diseasessuch as Alzheimer's disease, for example. The compounds described mayalso be used for the treatment of tumours, particularly for modifyingtumour invasion and also metastasisation; examples here are their use intreating T-cell lymphomas, acute lymphoblastic leukaemia, cell-basedpancreatic carcinomas, basal cell carcinomas or breast cancers. Otherindications are stroke, ischaemia of various origins, Parkinson'sdisease and migraine. In addition, further indications includefollicular and epidermal hyperkeratoses, increased keratinocyteproliferation, psoriasis, encephalomyelitis, glomerulonephritis,lipodystrophies, as well as psychosomatic, depressive andneuropsychiatric diseases of all kinds.

The compounds according to the invention may also be used in conjunctionwith other active substances. Therapeutic agents which are suitable forsuch combinations include, for example, antidiabetics, such asmetformin, sulphonylureas (e.g. glibenclamide, tolbutamide,glimepiride), nateglinide, repaglinide, thiazolidinedione (e.g.rosiglitazone, pioglitazone), PPAR-gamma agonists (e.g. GI 262570) andantagonists, PPAR-gamma/alpha modulators (e.g. KRP 297),alpha-glucosidase inhibitors (e.g. acarbose, voglibose), other DPPIVinhibitors, alpha2 antagonists, insulin and insulin analogues, GLP-1 andGLP-1 analogues (e.g. exendin-4) or amylin. Also, SGLT2 inhibitors suchas T-1095, inhibitors of protein tyrosine phosphatase 1, substanceswhich influence deregulated glucose production in the liver, such ase.g. inhibitors of glucose-6-phosphatase, orfructose-1,6-bisphosphatase, glycogen phosphorylase, glucagon receptorantagonists and inhibitors of phosphoenol—pyruvate carboxykinase,glycogen synthase kinase or pyruvate dehydrokinase, lipid loweringagents, such as HMG-CoA-reductase inhibitors (e.g. simvastatin,atorvastatin), fibrates (e.g. bezafibrate, fenofibrate), nicotinic acidand its derivatives, PPAR-alpha agonists, PPAR-delta agonists, ACATinhibitors (e.g. avasimibe) or cholesterol resorption inhibitors such asfor example ezetimibe, bile acid-binding substances such as for examplecholestyramine, inhibitors of ileac bile acid transport, HDL-raisingcompounds such as for example inhibitors of CETP or regulators of ABC1or active substances for the treatment of obesity, such as e.g.sibutramine or tetrahydrolipostatin, dexfenfluramine, axokine,antagonists of the cannabinoid1 receptor, MCH-1 receptor antagonists,MC4 receptor agonists, NPY5 or NPY2 antagonists or β₃-agonists such asSB-418790 or AD-9677 as well as agonists of the 5HT2c receptor.

It is also possible to combine the compounds with drugs for treatinghigh blood pressure such as e.g. AII antagonists or ACE inhibitors,diuretics, β-blockers, Ca-antagonists, etc., or combinations thereof.

The dosage required to achieve such an effect is expediently, byintravenous route, 1 to 100 mg, preferably 1 to 30 mg, and by oral route1 to 1000 mg, preferably 1 to 100 mg, in each case 1 to 4 times a day.For this purpose, the compounds of formula I prepared according to theinvention, optionally combined with other active substances, may beincorporated together with one or more inert conventional carriersand/or diluents, e.g. with corn starch, lactose, glucose,microcrystalline cellulose, magnesium stearate, polyvinylpyrrolidone,citric acid, tartaric acid, water, water/ethanol, water/glycerol,water/sorbitol, water/polyethylene glycol, propylene glycol,cetylstearyl alcohol, carboxymethylcellulose or fatty substances such ashard fat or suitable mixtures thereof into conventional galenicpreparations such as plain or coated tablets, capsules, powders,suspensions or suppositories.

The Examples that follow are intended to illustrate the invention:

Preparation of the starting compounds:

EXAMPLE I 1,3-dimethyl-7-(2,6-dicyano-benzyl)-8-bromo-xanthine

A mixture of 555 mg of 8-bromotheophyllin and 0.39 ml of Hünig base in 9ml N,N-dimethylformamide is combined with 600 mg of2-bromomethyl-isophthalonitrile and stirred overnight at ambienttemperature. For working up the reaction mixture is poured onto water.The precipitate formed is suction filtered, washed with water and dried.

Yield: 686 mg (83% of theory)

R_(f) value: 0.56 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=399, 401 [M+H]⁺

The following compounds are obtained analogously to Example I:

(1) 3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine

Mass spectrum (ESI⁺): m/z=269, 271 [M+H]⁺

(2) 3-methyl-7-(2-cyano-benzyl)-8-chloro-xanthine

Mass spectrum (ESI⁺): m/z=316, 318 [M+H]⁺

(3) 1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-bromo-xanthine

Mass spectrum (ESI⁺): m/z=415, 417 [M+H]⁺

(4) 3-methyl-7-[(2-trimethylsilanyl-ethoxy)methyl]-8-bromo-xanthine

(Carried out in the presence of potassium carbonate)

Mass spectrum (ESI⁺): m/z=375, 377 [M+H]⁺

(5) 3-methyl-7-(3-methyl-2-buten-1-yl)-8-bromo-xanthine

Mass spectrum (ESI⁺): m/z=313, 315 [M+H]⁺

(6) 3-methyl-7-(2,3-dimethyl-2-buten-1-yl)-8-bromo-xanthine

R_(f) value: 0.43 (silica gel, methylene chloride/methanol=9:1)

Mass spectrum (ESI⁺): m/z=327, 329 [M+H]⁺

(7) 3-methyl-7-(2-butyn-1-yl)-8-bromo-xanthine

R_(f) value: 0.72 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=297/299 [M+H]⁺

(8) 3-methyl-7-((E)-2-buten-1-yl)-8-bromo-xanthine

(The product is contaminated with approx. 10-20% of Z compound)

R_(f) value: 0.55 (silica gel, cyclohexane/ethyl acetate/methanol=6:3:1)

Mass spectrum (ESI⁺): m/z=299, 301 [M+H]⁺

(9) 3-methyl-7-[(1-cyclopenten-1-yl)methyl]-8-bromo-xanthine

Mass spectrum (ESI⁺): m/z=325, 327 [M+H]⁺

(10)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-[(1-cyclopenten-1-yl)methyl]-8-bromo-xanthine

Mass spectrum (ESI⁺): m/z=443, 445 [M+H]⁺

(11)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-bromo-xanthine

(product contains approx. 25% of Z isomer)

Mass spectrum (ESI⁺): m/z=417, 419 [M+H]⁺

(12)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-(2-methyl-allyl)-8-bromo-xanthine

R_(f) value: 0.71 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=417, 419 [M+H]⁺

(13)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-(3-bromo-allyl)-8-bromo-xanthine

R_(f) value: 0.68 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=481, 483, 485 [M+H]⁺

(14)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-[(furan-2-yl)methyl]-8-bromo-xanthine

R_(f) value: 0.60 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=443, 445 [M+H]⁺

(15)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-(2-chloro-allyl)-8-bromo-xanthine

R_(f) value: 0.77 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=437, 439, 441 [M+H]⁺

(16)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-((Z)-2-methyl-2-buten-1-yl)-8-bromo-xanthine

R_(f) value: 0.77 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=431, 433 [M+H]⁺

(17)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-((E)-2-methyl-2-buten-1-yl)-8-bromo-xanthine

R_(f) value: 0.77 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=431, 433 [M+H]⁺

(18)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-(1-phenylsulphanyl-butyl)-8-bromo-xanthine

R_(f) value: 0.83 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=527, 529 [M+H]⁺

(19) 3-methyl-7-(3-methyl-1-phenylsulphanyl-butyl)-8-bromo-xanthine

(The [(1-chloro-3-methyl-butyl)sulphanyl]-benzene used as startingmaterial for the reaction is obtained by chlorination of[(3-methyl-butyl)sulphanyl]-benzene with N-chloro-succinimide in carbontetrachloride)

R_(f) value: 0.38 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=423, 425 [M+H]⁺

(20) 1,3-dimethyl-7-(2-bromo-benzyl)-8-chloro-xanthine

R_(f) value: 0.50 (silica gel, cyclohexane/ethyl acetate=1:1)

(21) 1,3-dimethyl-7-(2-chloro-benzyl)-8-chloro-xanthine

R_(f) value: 0.50 (silica gel, cyclohexane/ethyl acetate=1:1)

(22) 3-cyclopropyl-7-(2-butyn-1-yl)-8-bromo-xanthine

R_(f) value: 0.45 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:1)

Mass spectrum (ESI⁺): m/z=223/225 [M+H]⁺

EXAMPLE II1-(2-{2-[(ethoxycarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

63 mg of ethyl bromoacetate are added to a mixture of 200 mg of1-[2-(2-hydroxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthineand 63 mg of potassium carbonate in 3 ml N,N-dimethylformamide. Thereaction mixture is stirred for five hours at ambient temperature. Forworking up it is combined with water and the precipitate formed issuction filtered, washed with water and dried for three hours at 80° C.in the drying cupboard.

Yield: 216 mg (94% of theory)

Mass spectrum (ESI⁺): m/z=653 [M+H]⁺

The following compounds are obtained analogously to Example II:

(1)1-(2-{2-[(aminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=624 [M+H]⁺

(2)1-(2-{3-[(methylsulphanyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.20 (silica gel, cyclohexane/ethyl acetate=6:4)

Mass spectrum (ESI⁺): m/z=627 [M+H]⁺

(3)1-(2-{3-[(ethoxycarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.50 (silica gel, cyclohexane/ethyl acetate=3:7)

(4)1-(2-{2-[(methylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=638 [M+H]⁺

(5)1-(2-{2-[(dimethylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=652 [M+H]⁺

(6)1-(2-{3-[(methoxycarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=639 [M+H]⁺

(7)1-(2-{2-[(ethylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=636 [M+H]⁺

(8)1-(2-{2-[(methylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-[(1-cyclopenten-1-yl)methyl]-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=650 [M+H]⁺

(9)1-(2-{2-[(methylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=622 [M+H]⁺

(10)1-(2-{2-[(aminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=608 [M+H]⁺

(11)1-(2-{2-[(methoxycarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=623 [M+H]⁺

(12)1-(2-{2-[(isopropyloxycarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=667 [M+H]⁺

(13)1-(2-{2-[(methylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=622 [M+H]⁺

(14)1-(2-{2-[(methylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(product contains some Z isomer)

R_(f) value: 0.35 (silica gel, cyclohexane/ethyl acetate/methanol=5:4:1)

Mass spectrum (ESI⁺): m/z=624 [M+H]⁺

(15)1-(2-{2-[(ethylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=636 [M+H]⁺

(16)1-(2-{2-[(methylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=622 [M+H]⁺

(17)1-(2-{2-[(methoxycarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=639 [M+H]⁺

(18)1-(2-{2-[(methylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=638 [M+H]⁺

(19) 2-(2-acetyl-phenoxy)-N-ethyl-acetamide

Mass spectrum (ESI⁺): m/z=222 [M+H]⁺

(20)1-{2-[2-(1-methoxycarbonyl-ethoxy)-phenyl]-2-oxo-ethyl}-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=637 [M+H]⁺

(21)1-{2-[2-(1-aminocarbonyl-ethoxy)-phenyl]-2-oxo-ethyl}-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=622 [M+H]⁺

(22) 2-(2-acetyl-phenoxy)-N-methyl-acetamide

Mass spectrum (ESI⁺): m/z=208 [M+H]⁺

(23)1-{2-[2-(2-oxo-propoxy)-phenyl]-2-oxo-ethyl}-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=607 [M+H]⁺

(24)1-{2-[2-(1-ethoxycarbonyl-1-methyl-ethoxy)-phenyl]-2-oxo-ethyl}-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=665 [M+H]⁺

(25)1-{2-[2-cyanomethoxy-phenyl]-2-oxo-ethyl}-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=590 [M+H]⁺

(26)1-(2-{2-[(methylsulphanyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=611 [M+H]⁺

(27)1-{[2-(tert.-butylcarbonyl)-benzofuran-3-yl]methyl}-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(Formed as main product when1-[2-(2-hydroxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthineis reacted with 1-chloro-3,3-dimethyl-butan-2-one)

Mass spectrum (ESI⁺): m/z=631 [M+H]⁺

EXAMPLE III1-[2-(2-hydroxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

1.30 g of 3-tert.-butyloxycarbonylamino-piperidine are added to amixture of 2.51 g of1-[2-(2-hydroxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthineand 880 mg of sodium carbonate in 8 ml of dimethylsulphoxide. Thereaction mixture is stirred for 18 hours at 60° C. For working up it iscombined with water and the precipitate formed is suction filtered. Thesolid crude product is dissolved in ethyl acetate, the solution is driedover magnesium sulphate and evaporated down. The flask residue ischromatographed through a silica gel column with cyclohexane/ethylacetate (10:1 to 1:1) as eluant.

Yield: 2.56 g (91% of theory)

Mass spectrum (ESI⁺): m/z=567 [M+H]⁺

The following compounds are obtained analogously to Example III:

(1)3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=433 [M+H]⁺

(2)1-(1-methyl-2-oxo-2-phenyl-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=565 [M+H]⁺

(3)3-methyl-7-(2-cyano-benzyl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.90 (silica gel, methylene chloride/methanol=9:1)

Mass spectrum (ESI⁺): m/z=478 [M−H]⁻

(4)1-methyl-3-[(methoxycarbonyl)methyl]-7-(2-cyano-benzyl)-8-[3-(tert.-butyloxycarbonyl-amino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=552 [M+H]⁺

(5)1-methyl-3-cyanomethyl-7-(2-cyano-benzyl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=519 [M+H]⁺

(6)1-methyl-3-(2-propyn-1-yl)-7-(2-cyano-benzyl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=518 [M+H]⁺

(7)1-[2-(3-nitro-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.25 (silica gel, cyclohexane/ethyl acetate/methanol=7:2:1)

Mass spectrum (ESI⁺): m/z=596 [M+H]⁺

(8)1-methyl-3-(2-propen-1-yl)-7-(2-cyano-benzyl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=520 [M+H]⁺

(9)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=535 [M+H]⁺

(10)1-[2-(2-nitro-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.52 (silica gel, cyclohexane/ethyl acetate=3:7)

Mass spectrum (ESI⁺): m/z=596 [M+H]⁺

(11)1-methyl-3-phenyl-7-(2-cyano-benzyl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=556 [M+H]⁺

(12)1-[2-(2-nitro-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=596 [M+H]⁺

(13)1-[(cinnolin-4-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxy-carbonylamino)-piperidin-1-yl]-xanthinemixed with1-[(1,4-dihydro-cinnolin-4-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.62 (silica gel, ethyl acetate)

(14)1-({4-oxo-3-[(2-trimethylsilanyl-ethoxy)methyl]-3,4-dihydro-phthalazin-1-yl}methyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(Carried out with potassium carbonate in the presence of Hünig base)

R_(f) value: 0.27 (silica gel, cyclohexane/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=720 [M+H]⁺

(15)1-[(isoquinolin-3-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxy-carbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.31 (silica gel, ethyl acetate/petroleum ether=7:3)

Mass spectrum (ESI⁺): m/z=574 [M+H]⁺

(16)1-[(3-methyl-4-oxo-3,4-dihydro-phthalazin-1-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.45 (silica gel, methylene chloride/methanol/conc. aqueousammonia=95:5)

Mass spectrum (ESI⁺): m/z=605 [M+H]⁺

(17)3-methyl-7-(2,3-dimethyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(Carried out with potassium carbonate)

R_(f) value: 0.42 (silica gel, methylene chloride/methanol=20:1)

Mass spectrum (ESI⁺): m/z=447 [M+H]⁺

(18)3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(Carried out with potassium carbonate)

Melting point: 235-237° C.

Mass spectrum (ESI⁺): m/z=417 [M+H]⁺

(19)1-[(quinolin-4-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonyl-amino)-piperidin-1-yl]-xanthine

(Carried out with potassium carbonate)

R_(f) value: 0.36 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=558 [M+H]⁺

(20)1-[(isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonyl-amino)-piperidin-1-yl]-xanthine

(Carried out with potassium carbonate)

R_(f) value: 0.71 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=558 [M+H]⁺

(21)1-[(isoquinolin-1-yl)methyl]-3-methyl-7-((E)-2-buten-1-yl)-8-[3-(tert.-butyloxy-carbonylamino)-piperidin-1-yl]-xanthine

(Carried out with potassium carbonate; the product contains approx. 20%of Z isomer)

R_(f) value: 0.24 (silica gel, ethyl acetate/petroleum ether=1:1)

Mass spectrum (ESI⁺): m/z=560 [M+H]⁺

(22)3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(Carried out with potassium carbonate)

R_(f) value: 0.64 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=417 [M+H]⁺

(23)3-methyl-7-(2-butyn-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(Carried out with potassium carbonate)

R_(f) value: 0.64 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=417 [M+H]⁺

(24)3-methyl-7-((E)-2-buten-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(product contains approx. 15% of Z isomer)

R_(f) value: 0.35 (silica gel, cyclohexane/ethyl acetate=3:7)

Mass spectrum (ESI⁺): m/z=419 [M+H]⁺

(25)3-methyl-7-((E)-2-buten-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(product contains approx. 15% of Z isomer)

R_(f) value: 0.35 (silica gel, cyclohexane/ethyl acetate=3:7)

Mass spectrum (ESI⁺): m/z=419 [M+H]⁺

(26)1-[2-(2-hydroxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=551 [M+H]⁺

(27)1-[2-(2-amino-phenyl)-2-oxo-ethyl]-3-methyl-7-[(1-cyclopenten-1-yl)methyl]-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=578 [M+H]⁺

(28)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-[(1-cyclopenten-1-yl)methyl]-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=563 [M+H]⁺

(29)1-[2-(2-hydroxy-phenyl)-2-oxo-ethyl]-3-methyl-7-[(1-cyclopenten-1-yl)methyl]-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=579 [M+H]⁺

(30)1-methyl-3-isopropyl-7-(2-cyano-benzyl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=522 [M+H]⁺

(31)1-[2-(2-hydroxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=551 [M+H]⁺

(32)1-[2-(2-amino-phenyl)-2-oxo-ethyl]-3-methyl-7-((E)-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(product contains approx. 10% of Z isomer)

R_(f) value: 0.20 (silica gel, cyclohexane/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=552 [M+H]⁺

(33)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-[3-(tert.-butyloxy-carbonylamino)-piperidin-1-yl]-xanthine

(product contains approx. 25% of Z isomer)

Mass spectrum (ESI⁺): m/z=537 [M+H]⁺

(34)1-[2-(2-hydroxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine(35)1-[2-(2-hydroxy-phenyl)-2-oxo-ethyl]-3-methyl-7-((E)-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(product contains some Z isomer)

R_(f) value: 0.30 (silica gel, cyclohexane/ethyl acetate=4:6)

Mass spectrum (ESI⁺): m/z=553 [M+H]⁺

(36)1-[2-(2-hydroxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=551 [M+H]⁺

(37)1-[2-(2-amino-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxy-carbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.50 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=550 [M+H]⁺

(38)1-[2-(2-hydroxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=567 [M+H]⁺

(39)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonyl-amino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=535 [M+H]⁺

(40)1-methyl-3-[(2-trimethylsilanyl-ethoxy)methyl]-7-(2-cyano-benzyl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=610 [M+H]⁺

(41)3-methyl-7-(2-butyn-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(Carried out with potassium carbonate)

R_(f) value: 0.52 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=417 [M+H]⁺

(42)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-(2-methyl-allyl)-8-[3-(tert.-butyloxycarbonyl-amino)-piperidin-1-yl]-xanthine

R_(f) value: 0.46 (silica gel, methylene chloride/methanol=95:5)

(43)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-(3-bromo-allyl)-8-[3-(tert.-butyloxycarbonyl-amino)-piperidin-1-yl]-xanthine

R_(f) value: 0.22 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=601, 603 [M+H]⁺

(44)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-[(furan-2-yl)methyl]-8-[3-(tert.-butyloxycarbonyl-amino)-piperidin-1-yl]-xanthine

R_(f) value: 0.41 (silica gel, methylene chloride/methanol=95:5)

(45)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-(2-chloro-allyl)-8-[3-(tert.-butyloxycarbonyl-amino)-piperidin-1-yl]-xanthine

R_(f) value: 0.49 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=557, 559 [M+H]⁺

(46)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-[(S)-3-(tert.-butyloxy-carbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=535 [M+H]⁺

(47)1-[2-(2-amino-phenyl)-2-oxo-ethyl]-3-methyl-7-((E)-2-buten-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.40 (silica gel, cyclohexane/ethyl acetate=4:6)

Mass spectrum (ESI⁺): m/z=552 [M+H]⁺

(48)1-[2-(2-nitro-phenyl)-2-oxo-ethyl]-3-methyl-7-((E)-2-buten-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.50 (silica gel, cyclohexane/ethyl acetate=1:2)

(49)1-[2-(2-nitro-phenyl)-2-oxo-ethyl]-3-methyl-7-((E)-2-buten-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=582 [M+H]⁺

(50)1-[2-(2-nitro-3-methoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=626 [M+H]⁺

(51)1-(2-{2-oxo-3-[(2-trimethylsilanyl-ethoxy)methyl]-2,3-dihydro-benzooxazol-7-yl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=738 [M+H]⁺

(52)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-((Z)-2-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.48 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=551 [M+H]⁺

(53)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-((E)-2-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=551 [M+H]⁺

(54)1-(2-{2-oxo-3-[(2-trimethylsilanyl-ethoxy)methyl]-2,3-dihydro-benzooxazol-4-yl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.40 (silica gel, petroleum ether/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=722 [M+H]⁺

(55)1-[2-(2,2-difluoro-benzo[1,3]dioxol-4-yl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=615 [M+H]⁺

(56)1-[2-(2,2-difluoro-benzo[1,3]dioxol-4-yl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=615 [M+H]⁺

(57)1-[(1-methyl-1H-indol-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxy-carbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.80 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=560 [M+H]⁺

(58)1-[(quinolin-3-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonyl-amino)-piperidin-1-yl]-xanthine

R_(f) value: 0.50 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=558 [M+H]⁺

(59)1-{[1-(tert.-butyloxycarbonylamino)-1H-indol-2-yl]methyl}-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.40 (silica gel, petroleum ether/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=646 [M+H]⁺

(60)1-[(2-methyl-1-[(2-trimethylsilanyl-ethoxy)methyl]-1H-benzoimidazol-5-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine(mixed with1-[(2-methyl-3-[(2-trimethylsilanyl-ethoxy)methyl]-3H-benzoimidazol-5-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine)

R_(f) value: 0.15 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=691 [M+H]⁺

(61)1-[2-(quinolin-8-yl-]-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxy-carbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.35 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=586 [M+H]⁺

(62)1-[(1-[(2-trimethylsilanyl-ethoxy)methyl]-1H-benzoimidazol-5-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine(mixed with1-[(3-[(2-trimethylsilanyl-ethoxy)methyl]-3H-benzoimidazol-5-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine)

R_(f) value: 0.23 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=677 [M+H]⁺

(63)1-[(pyrazolo[1,5-a]pyridin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.46 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=547 [M+H]⁺

(64)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-((E)-1-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.48 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=537 [M+H]⁺

(65)1-{2-[1-(tert.-butyloxycarbonyl)-1H-indol-7-yl]-2-oxo-ethyl}-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.38 (silica gel, petroleum ether/ethyl acetate=1:1)

(66)1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(3-methyl-1-buten-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.40 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=588 [M+H]⁺

(67)1,3-dimethyl-7-(2-bromo-benzyl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.40 (silica gel, cyclohexane/ethyl acetate=1:1)

(68)1,3-dimethyl-7-(2-chloro-benzyl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.42 (silica gel, cyclohexane/ethyl acetate=1:1)

(69)1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-cyano-benzyl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=635 [M+H]⁺

R_(f) value: 0.40 (silica gel, cyclohexane/ethyl acetate=3:7)

(70)3-cyclopropyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=443 [M+H]⁺

R_(f) value: 0.70 (silica gel, ethyl acetate)

(71)3-cyclopropyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.35 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:1)

Mass spectrum (ESI⁺): m/z=443 [M+H]⁺

(72)1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-chloro-benzyl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=644, 646 [M+H]⁺

R_(f) value: 0.39 (silica gel, cyclohexane/ethyl acetate=1:1)

(73)1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-bromo-benzyl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=644, 646 [M+H]⁺

(74)1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-chloro-benzyl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Prepared by reacting (4-methyl-quinazolin-2-yl)-methylchloride and3-methyl-7-(2-chlorobenzyl)-8-bromo-xanthine and subsequently reactingwith (R)-3-(tert.-butyloxycarbonylamino)-piperidine

Mass spectrum (ESI⁺): m/z=645, 647 [M+H]⁺

(75)1-[(4-phenyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-chloro-benzyl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Prepared by reacting (4-phenyl-quinazolin-2-yl)-methylchloride and3-methyl-7-(2-chlorobenzyl)-8-bromo-xanthine and subsequently reactingwith (R)-3-(tert.-butyloxycarbonylamino)-piperidine

Mass spectrum (ESI⁺): m/z=707, 709 [M+H]⁺

EXAMPLE IV1-[2-(2-hydroxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine

Prepared by treating1-[2-(2-methoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthinewith boron tribromide in methylene chloride. The desired product iscontaminated with approx. 20%1-[2-(2-hydroxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-bromo-3-methyl-butyl)-8-chloro-xanthine.

Mass spectrum (ESI⁺): m/z=403, 405 [M+H]⁺

The following compounds are obtained analogously to Example IV:

(1)1-[2-(2-hydroxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-bromo-xanthine

(product is contaminated with approx. 20%1-[2-(2-hydroxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-bromo-2-buten-1-yl)-8-bromo-xanthine)

Mass spectrum (ESI⁺): m/z=431, 433 [M+H]⁺

(2)1-[2-(2-hydroxy-phenyl)-2-oxo-ethyl]-3-methyl-7-[(1-cyclopenten-1-yl)methyl]-8-bromo-xanthine

Mass spectrum (ESI⁺): m/z=459, 461 [M+H]⁺

(3)1-[2-(2-hydroxy-phenyl)-2-oxo-ethyl]-3-methyl-7-((E)-2-buten-1-yl)-8-bromo-xanthine

(product contains some Z isomer)

R_(f) value: 0.60 (silica gel, cyclohexane/ethyl acetate=4:6)

Mass spectrum (ESI⁺): m/z=433, 435 [M+H]⁺

(4)1-[2-(2-hydroxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-bromo-xanthine

Mass spectrum (ESI⁺): m/z=447, 449 [M+H]⁺

EXAMPLE V1-[2-(2-methoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine

1.71 g of 2-bromo-1-(2-methoxy-phenyl)-ethanone are added to a mixtureof 2.00 g of 3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine and1.38 mg of potassium carbonate in 15 ml of N,N-dimethylformamide. Thereaction mixture is stirred for eight hours at ambient temperature.After aqueous working up the crude product is purified by chromatographythrough a silica gel column with cyclohexane/ethyl acetate (8:1 to 8:1)as eluant.

Yield: 2.61 g (84% of theory)

Mass spectrum (ESI⁺): m/z=417, 419 [M+H]⁺

The following compounds are obtained analogously to Example V:

(1)1-[2-(3-hydroxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(The reaction is carried out with2-bromo-1-[3-(tert.-butyldimethylsilanyloxy)-phenyl]-ethanone)

R_(f) value: 0.40 (silica gel, cyclohexane/ethyl acetate=3:7)

Mass spectrum (ESI⁺): m/z=567 [M+H]⁺

(2)1-(1-methyl-2-oxo-2-phenyl-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine

Mass spectrum (ESI⁺): m/z=401, 403 [M+H]⁺

(3) 1-(2-cyano-ethyl)-3-methyl-7-(2-cyano-benzyl)-8-chloro-xanthine

Mass spectrum (ESI⁺): m/z=391, 393 [M+Na]⁺

(4)1-(2-phenoxy-ethyl)-3-methyl-7-(2-cyano-benzyl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.90 (silica gel, methylene chloride/methanol=9:1)

Mass spectrum (ESI⁺): m/z=600 [M+H]⁺

(5)1-(2-phenyl-2-oxo-ethyl)-3-[(2-trimethylsilanyl-ethoxy)methyl]-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=667 [M+H]⁺

(6)1-(2-methoxy-ethyl)-3-methyl-7-(2-cyano-benzyl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.90 (silica gel, methylene chloride/methanol=9:1)

Mass spectrum (ESI⁺): m/z=538 [M+H]⁺

(7)1-methyl-3-[(2-trimethylsilanyl-ethoxy)methyl]-7-(2-cyano-benzyl)-xanthine

R_(f) value: 0.60 (silica gel, cyclohexane/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=412 [M+H]⁺

(8)1-[2-(3-nitro-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine

R_(f) value: 0.40 (silica gel, cyclohexane/ethyl acetate/methanol=7:2:1)

Mass spectrum (ESI⁺): m/z=432, 434 [M+H]⁺

(9)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-[(2-trimethylsilanyl-ethoxy)methyl]-8-bromo-xanthine

Mass spectrum (ESI⁺): m/z=493, 495 [M+H]⁺

(10)1-[2-(2-nitro-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine

R_(f) value: 0.64 (silica gel, cyclohexane/ethyl acetate=3:7)

Mass spectrum (ESI⁺): m/z=432, 434 [M+H]⁺

(11)1-[2-(2-nitro-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-bromo-xanthine

Mass spectrum (ESI⁺): m/z=476, 478 [M+H]⁺

(12)1-[(quinolin-2-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxy-carbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.45 (silica gel, ethyl acetate/petroleum ether=7:3)

Mass spectrum (ESI⁺): m/z=574 [M+H]⁺

(13)1-[(2-oxo-2H-chromen-4-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(The starting material 4-bromomethyl-chromen-2-one is preparedanalogously to Kimura et al., Chem. Pharm. Bull. 1982, 30, 552-558.)

R_(f) value: 0.52 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=591 [M+H]⁺

(14)1-[(1-methyl-2-oxo-1,2-dihydro-quinolin-4-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.54 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=604 [M+H]⁺

(15)1-[(quinazolin-4-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Melting point: 195-197° C.

Mass spectrum (ESI⁺): m/z=575 [M+H]⁺

(16)1-[(5-methyl-3-phenyl-isoxazol-4-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.40 (silica gel, cyclohexane/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=604 [M+H]⁺

(17)1-[(3-phenyl-[1,2,4]oxadiazol-5-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.18 (silica gel, petroleum ether/ethyl acetate=2:1)

Mass spectrum (ESI⁺): m/z=591 [M+H]⁺

(18)1-[(4-phenyl-pyridin-2-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.53 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=600 [M+H]⁺

(19)1-[(5-phenyl-pyridin-2-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.73 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=600 [M+H]⁺

(20)1-[2-(3-methylsulphanyl-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.43 (silica gel, cyclohexane/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=597 [M+H]⁺

(21)1-[2-(3-methoxycarbonyl-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(Carried out in N-methylpyrrolidin-2-one at 60° C.)

R_(f) value: 0.27 (silica gel, methylene chloride/methanol=20:1)

Mass spectrum (ESI⁺): m/z=609 [M+H]⁺

(22)1-[2-(2-ethoxycarbonyl-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(Carried out in N-methylpyrrolidin-2-one at 60° C.)

R_(f) value: 0.35 (silica gel, methylene chloride/methanol=20:1)

Mass spectrum (ESI⁺): m/z=623 [M+H]⁺

(23)1-[2-(2,6-dimethoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(Carried out in N-methylpyrrolidin-2-one at 60° C.)

R_(f) value: 0.53 (silica gel, methylene chloride/methanol=20:1)

Mass spectrum (ESI⁺): m/z=611 [M+H]⁺

(24)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-(2,3-dimethyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(Carried out in N-methylpyrrolidin-2-one at 60° C.)

R_(f) value: 0.38 (silica gel, methylene chloride/methanol=20:1)

Mass spectrum (ESI⁺): m/z=565 [M+H]⁺

(25)1-((E)-3-phenyl-allyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonyl-amino)-piperidin-1-yl]-xanthine

R_(f) value: 0.54 (silica gel, methylene chloride/methanol/conc. aqueousammonia=95:5:0.1)

Mass spectrum (ESI⁺): m/z=549 [M+H]⁺

(26)1-[(1-benzo[b]thiophen-3-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.75 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=579 [M+H]⁺

(27)1-{[1-(tert.-butyloxycarbonyl)-indol-3-yl]methyl}-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.61 (silica gel, methylene chloride/methanol=9:1)

Mass spectrum (ESI⁺): m/z=662 [M+H]⁺

(28)1-[(biphenyl-4-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.68 (silica gel, cyclohexane/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=599 [M+H]⁺

(29)1-[(1-naphthyl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.83 (silica gel, ethyl acetate/petroleum ether=4:1)

Mass spectrum (ESI⁺): m/z=557 [M+H]⁺

(30)1-[(1-methyl-2-oxo-1,2-dihydro-quinolin-4-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.25 (silica gel, ethyl acetate/petroleum ether=4:1)

Mass spectrum (ESI⁺): m/z=588 [M+H]⁺

(31)1-(2-cyclohexyl-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Melting point: 163-165° C.

Mass spectrum (ESI⁺): m/z=557 [M+H]⁺

(32)1-(3,3-dimethyl-2-oxo-butyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.95 (silica gel, ethyl acetate/petroleum ether=4:1)

Mass spectrum (ESI⁺): m/z=531 [M+H]⁺

(33)1-[(quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonyl-amino)-piperidin-1-yl]-xanthine

R_(f) value: 0.40 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=559 [M+H]⁺

(34)1-[(2-methyl-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.80 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=571 [M+H]⁺

(35)1-[(5-nitro-isoquinolin-1-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.54 (silica gel, methylene chloride/methanol=95:5)

(36)1-(2-dimethylamino-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.23 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=518 [M+H]⁺

(37)1-[2-(piperidin-1-yl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.44 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=558 [M+H]⁺

(38)1-[(2-methyl-1-oxo-1,2-dihydro-isoquinolin-4-yl)methyl]-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.25 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=588 [M+H]⁺

(39)1-[(2-methyl-1-oxo-1,2-dihydro-isoquinolin-4-yl)methyl]-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.30 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=604 [M+H]⁺

(40)1-[(2-methoxy-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.75 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=587 [M+H]⁺

(41)1-[(4-methoxy-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.80 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=587 [M+H]⁺

(42)1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.56 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=572 [M+H]⁺

(43)1-[2-(2,3-dimethoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.83 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=611 [M+H]⁺

(44)1-[(5-nitro-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxy-carbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.78 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=602 [M+H]⁺

(45)1-[2-(pyrrolidin-1-yl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.39 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=544 [M+H]⁺

(46)1-[(4-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.56 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=572 [M+H]⁺

(47)1-[(2-naphthyl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.78 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=557 [M+H]⁺

(48)1-cyanomethyl-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.80 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=456 [M+H]⁺

(49)1-[(quinolin-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonyl-amino)-piperidin-1-yl]-xanthine

R_(f) value: 0.40 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=558 [M+H]⁺

(50)1-[(3-methoxy-naphthalen-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.83 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=587 [M+H]⁺

(51)1-[2-(2,3-dihydro-benzo[1,4]dioxin-5-yl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.38 (silica gel, ethyl acetate/petroleum ether=1:1)

Mass spectrum (ESI⁺): m/z=609 [M+H]⁺

(52)1-[2-(3-methyl-2-oxo-2,3-dihydro-benzooxazol-7-yl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(Carried out with potassium-tert. butoxide in dimethylsulphoxide)

R_(f) value: 0.48 (silica gel, ethyl acetate/petroleum ether=2:1)

Mass spectrum (ESI⁺): m/z=622 [M+H]⁺

(53)1-[2-(benzo[1,3]dioxol-4-yl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=595 [M+H]⁺

(54)1-[(quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonyl-amino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=559 [M+H]⁺

(55)1-[(quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[(S)-3-(tert.-butyloxycarbonyl-amino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=559 [M+H]⁺

(56)1-[(quinazolin-2-yl)methyl]-3-methyl-7-((E)-2-buten-1-yl)-8-[(S)-3-(tert.-butyloxy-carbonylamino)-piperidin-1-yl]-xanthine

(product contains approx. 15% of Z isomer)

R_(f) value: 0.30 (silica gel, ethyl acetate/cyclohexane=8:2)

Mass spectrum (ESI⁺): m/z=561 [M+H]⁺

(57)1-[(quinazolin-2-yl)methyl]-3-methyl-7-((E)-2-buten-1-yl)-8-[(R)-3-(tert.-butyloxy-carbonylamino)-piperidin-1-yl]-xanthine

(product contains approx. 15% of Z isomer)

R_(f) value: 0.30 (silica gel, ethyl acetate/cyclohexane=8:2)

Mass spectrum (ESI⁺): m/z=561 [M+H]⁺

(58)1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-((E)-2-buten-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(product contains approx. 17% of Z isomer)

R_(f) value: 0.58 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=574 [M+H]⁺

(59)1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-((E)-2-buten-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(product contains approx. 17% of Z isomer)

R_(f) value: 0.58 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=574 [M+H]⁺

(60)1-[2-(2-methoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-bromo-xanthine

Mass spectrum (ESI⁺): m/z=445, 447 [M+H]⁺

(61)1-[2-(2-nitro-phenyl)-2-oxo-ethyl]-3-methyl-7-[(1-cyclopenten-1-yl)methyl]-8-bromo-xanthine

Mass spectrum (ESI⁺): m/z=488, 490 [M+H]⁺

(62)1-[2-(2-methoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-[(1-cyclopenten-1-yl)methyl]-8-bromo-xanthine

Mass spectrum (ESI⁺): m/z=473, 475 [M+H]⁺

(63)1-[(isoquinolin-1-yl)methyl]-3-[(methoxycarbonyl)methyl]-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.35 (silica gel, methylene chloride/methanol=95:5)

(64)1-[2-(2-nitro-phenyl)-2-oxo-ethyl]-3-methyl-7-((E)-2-buten-1-yl)-8-bromo-xanthine

(product contains approx. 10% of Z isomer)

R_(f) value: 0.60 (silica gel, cyclohexane/ethyl acetate=4:6)

Mass spectrum (ESI⁺): m/z=462, 464 [M+H]⁺

(65)1-[2-(2-methoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-((E)-2-buten-1-yl)-8-bromo-xanthine

(product contains some Z isomer)

R_(f) value: 0.30 (silica gel, cyclohexane/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=447, 449 [M+H]⁺

(66)1-[2-(2-nitro-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-bromo-xanthine

R_(f) value: 0.77 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=460, 462 [M+H]⁺

(67)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-[(R)-3-(tert.-butyloxy-carbonylamino)-piperidin-1-yl]-xanthine

(product contains approx. 20% of Z isomer)

Mass spectrum (ESI⁺): m/z=537 [M+H]⁺

(68)1-[2-(2-methoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-bromo-xanthine

Mass spectrum (ESI⁺): m/z=461, 463 [M+H]⁺

(69) 1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-bromo-xanthine

R_(f) value: 0.61 (silica gel, cyclohexane/ethyl acetate=4:6)

(70)1-(2-{2-[(ethylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(product contains approx. 17% of Z isomer)

Mass spectrum (ESI⁺): m/z=638 [M+H]⁺

(71)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-[(S)-3-(tert.-butyloxy-carbonylamino)-piperidin-1-yl]-xanthine

(product contains approx. 18% of Z isomer)

R_(f) value: 0.35 (silica gel, cyclohexane/ethyl acetate=6:4)

Mass spectrum (ESI⁺): m/z=537 [M+H]⁺

(72)1-[2-(2-nitro-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.60 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=580 [M+H]⁺

(73)1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.52 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=572 [M+H]⁺

(74)1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=572 [M+H]⁺

(75)1-[(4-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=572 [M+H]⁺

(76)1-[(4-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=572 [M+H]⁺

(77)1-[(4-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-((E)-2-buten-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.52 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=574 [M+H]⁺

(78)1-[(4-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-((E)-2-buten-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.52 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=574 [M+H]⁺

(79)1-[2-(2,3-dihydro-benzo[1,4]dioxin-5-yl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.18 (silica gel, ethyl acetate/petroleum ether=1:1)

Mass spectrum (ESI⁺): m/z=593 [M+H]⁺

(80)1-[2-(2,3-dihydro-benzo[1,4]dioxin-5-yl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=593 [M+H]⁺

(81)1-[(4-methoxy-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.56 (silica gel, petroleum ether/ethyl acetate=1:2)

Mass spectrum (ESI⁺): m/z=587 [M+H]⁺

(82)1-[(4-methoxy-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=587 [M+H]⁺

(83)1-[2-(benzo[1,3]dioxol-4-yl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.86 (silica gel, ethyl acetate/petroleum ether=4:1)

Mass spectrum (ESI⁺): m/z=579 [M+H]⁺

(84)1-[2-(benzo[1,3]dioxol-4-yl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.86 (silica gel, ethyl acetate/petroleum ether=4:1)

Mass spectrum (ESI⁺): m/z=579 [M+H]⁺

(85)1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.48 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=573 [M+H]⁺

(86)1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.48 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=573 [M+H]⁺

(87)1-[2-(3-methyl-2-oxo-2,3-dihydro-benzooxazol-4-yl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.50 (silica gel, petroleum ether/ethyl acetate=1:2)

Mass spectrum (ESI⁺): m/z=622 [M+H]⁺

(88)1-(2-{2-[(ethylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=638 [M+H]⁺

(89)1-(2-{2-[(methylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=624 [M+H]⁺

(90)1-(2-{2-[(methylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=624 [M+H]⁺

(91)1-[2-(2-nitro-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.60 (silica gel, methylene chloride/methanol=95:5)

(92)1-[2-(2-nitro-3-methoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-bromo-xanthine

Mass spectrum (ESI⁺): m/z=506, 508 [M+H]⁺

(93)1-[(4-dimethylamino-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(Carried out in the presence of caesium carbonate)

R_(f) value: 0.40 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=602 [M+H]⁺

(94)1-(2-{2-oxo-3-[(2-trimethylsilanyl-ethoxy)methyl]-2,3-dihydro-benzooxazol-7-yl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-bromo-xanthine

R_(f) value: 0.75 (silica gel, ethyl acetate/petroleum ether=1:1)

Mass spectrum (ESI⁺): m/z=618, 620 [M+H]⁺

(95)1-[(imidazo[1,2-a]pyridin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.44 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=547 [M+H]⁺

(96)1-[(quinoxalin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonyl-amino)-piperidin-1-yl]-xanthine

R_(f) value: 0.50 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=559 [M+H]⁺

(97)1-[2-(1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzoimidazol-4-yl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.50 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=619 [M+H]⁺

(98)1-[(quinoxalin-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.35 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=559 [M+H]⁺

(99)1-(2-{2-oxo-3-[(2-trimethylsilanyl-ethoxy)methyl]-2,3-dihydro-benzooxazol-4-yl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-bromo-xanthine

R_(f) value: 0.30 (silica gel, petroleum ether/ethyl acetate=2:1)

Mass spectrum (ESI⁻): m/z=600, 602 [M−H]⁻

(100)1-[(3-methyl-quinoxalin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.44 (silica gel, petroleum ether/ethyl acetate=1:2)

Mass spectrum (ESI⁺): m/z=573 [M+H]⁺

(101)1-[(3-phenyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.85 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=634 [M+H]⁺

(102)1-[(3,4-dimethyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.60 (silica gel, ethyl acetate/methanol=3:1)

Mass spectrum (ESI⁺): m/z=586 [M+H]⁺

(103)1-[(benzofuran-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-[(R)-3-(tert.-butyl-oxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=547 [M+H]⁺

(104)1-{[4-(morpholin-4-yl)-quinazolin-2-yl]methyl}-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(Carried out in the presence of caesium carbonate)

R_(f) value: 0.28 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=644 [M+H]⁺

(105)1-{[4-(piperidin-1-yl)-quinazolin-2-yl]methyl}-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(Carried out in the presence of caesium carbonate)

R_(f) value: 0.35 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=642 [M+H]⁺

(106)1-({4-[4-(tert.-butyloxycarbonyl)-piperazin-1-yl]-quinazolin-2-yl}methyl)-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(Carried out in the presence of caesium carbonate)

R_(f) value: 0.50 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=743 [M+H]⁺

(107)1-{[4-(pyrrolidin-1-yl)-quinazolin-2-yl]methyl}-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(Carried out in the presence of caesium carbonate)

R_(f) value: 0.59 (silica gel, ethyl acetate/methanol/conc. aqueousammonia=95:5:0.1)

Mass spectrum (ESI⁺): m/z=628 [M+H]⁺

(108)1-[2-(1-ethoxycarbonyl-3-methyl-2-oxo-2,3-dihydro-1H-benzoimidazol-4-yl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.25 (silica gel, petroleum ether/ethyl acetate=1:2)

Mass spectrum (ESI⁺): m/z=677 [M+H]⁺

(109)1-[(4-cyano-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.77 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=582 [M+H]⁺

(110)1-[(imidazo[1,2-a]pyridine-3-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=547 [M+H]⁺

(111)1-[(8-methyl-imidazo[1,2-a]pyridin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.25 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=561 [M+H]⁺

(112)1-[(8-methoxy-quinolin-5-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.60 (silica gel, ethyl acetate/methanol=9:1)

Mass spectrum (ESI⁺): m/z=588 [M+H]⁺

(113)1-[(5-methoxy-quinolin-8-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.40 (silica gel, methylene chloride/methanol=20:1)

Mass spectrum (ESI⁺): m/z=588 [M+H]⁺

(114)1-[(4-phenyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=635 [M+H]⁺

(115)1-[(7-methyl-imidazo[1,2-a]pyridin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.50 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=561 [M+H]⁺

(116)1-(2-oxo-4-phenyl-butyl)-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=563 [M+H]⁺

(117)1-(2-{2-oxo-1,3-bis-[(2-trimethylsilanyl-ethoxy)methyl]-2,3-dihydro-1H-benzoimidazol-4-yl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxy-carbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.50 (silica gel, ethyl acetate/petroleum ether=1:1)

Mass spectrum (ESI⁺): m/z=851 [M+H]⁺

(118)1-[(3-difluoromethyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(By-product of the reaction of3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxy-carbonylamino)-piperidin-1-yl]-xanthinewith 1-chloromethyl-3-trifluoromethyl-3,4-dihydro-isoquinoline)

R_(f) value: 0.75 (aluminium oxide, petroleum ether/ethyl acetate=1:2)

Mass spectrum (ESI⁺): m/z=608 [M+H]⁺

(119)1-[2-(2,2-difluoro-benzo[1,3]dioxol-4-yl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-bromo-xanthine

Mass spectrum (ESI⁺): m/z=495, 497 [M+H]⁺

(120)1-[(3-methyl-imidazo[1,2-a]pyridin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.50 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=561 [M+H]⁺

(121)1-[(5-methyl-imidazo[1,2-a]pyridin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.50 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=561 [M+H]⁺

(122)1-[(6-methyl-imidazo[1,2-a]pyridin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.10 (silica gel, ethyl acetate/methanol=98:2)

Mass spectrum (ESI⁺): m/z=561 [M+H]⁺

(123)1-[(3-benzyl-imidazo[1,2-a]pyridin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.60 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=637 [M+H]⁺

(124)1-[(4-isopropyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.50 (silica gel, ethyl acetate/petroleum ether=8:2)

Mass spectrum (ESI⁺): m/z=601 [M+H]⁺

(125)1-[(2,3-dihydro-benzo[1,4]dioxin-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.53 (silica gel, ethyl acetate/petroleum ether=3:2)

(126)1-[(3-phenyl-imidazo[1,2-a]pyridin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.50 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=623 [M+H]⁺

(127)1-[2-(naphthalen-1-yl]-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.54 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=585 [M+H]⁺

(128)1-[(5-methoxy-isoquinolin-8-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.50 (silica gel, ethyl acetate/methanol=24:1)

Mass spectrum (ESI⁺): m/z=588 [M+H]⁺

(129)1-[(3-difluoromethyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(By-product of the reaction of3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxy-carbonylamino)-piperidin-1-yl]-xanthinewith 1-chloromethyl-3-trifluoromethyl-3,4-dihydro-isoquinoline)

R_(f) value: 0.75 (aluminium oxide, petroleum ether/ethyl acetate=1:2)

Mass spectrum (ESI⁺): m/z=608 [M+H]⁺

(130)1-{[1-(1-cyano-1-methyl-ethyl)-isoquinolin-3-yl]methyl}-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.75 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=625 [M+H]⁺

(132)1-methoxycarbonylmethyl-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonyl-amino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=489 [M+H]⁺

(133)1-[(4-phenyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=635 [M+H]⁺

(134)1-[(2,3-dimethyl-quinoxalin-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(Carried out in the presence of caesium carbonate)

R_(f) value: 0.40 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=587 [M+H]⁺

(135)1-[(4-phenyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.55 (silica gel, ethyl acetate/petroleum ether=8:2)

Mass spectrum (ESI⁺): m/z=635 [M+H]⁺

(136)1-[2-(quinolin-8-yl-]-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-bromo-xanthine

R_(f) value: 0.55 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=466, 468 [M+H]⁺

(137)1-[(3,4-dimethyl-6,7-dihydro-5H-[2]pyrindin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.65 (aluminium oxide, ethyl acetate/petroleum ether=3:1)

Mass spectrum (ESI⁺): m/z=576 [M+H]⁺

(138)1-[(3,4-dimethyl-5,6,7,8-tetrahydro-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.40 (aluminium oxide, methylene chloride/methanol=20:1)

Mass spectrum (ESI⁺): m/z=590 [M+H]⁺

(139)1-{2-[1-(tert.-butyloxycarbonyl)-1H-indol-4-yl]-2-oxo-ethyl}-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.55 (silica gel, petroleum ether/ethyl acetate=1:2)

Mass spectrum (ESI⁺): m/z=674 [M+H]⁺

(140)1-[(1-methyl-2-oxo-1,2-dihydro-quinolin-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (EI): m/z=587 [M]⁺

(141)1-({1-[(2-trimethylsilanyl-ethoxy)methyl]-2-oxo-1,2-dihydro-quinolin-6-yl}methyl)-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=704 [M+H]⁺

(142)1-[(2,3,8-trimethyl-quinoxalin-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=601 [M+H]⁺

(143)1-[(8-methyl-quinoxalin-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=573 [M+H]⁺

(144)1-[(4-methyl-phthalazin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.65 (silica gel, methylene chloride/methanol=9:1)

Mass spectrum (ESI⁺): m/z=573 [M+H]⁺

(145)1-[(4-bromo-3-methoxy-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.65 (silica gel, methylene chloride/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=666, 668 [M+H]⁺

(146)1-[(4-difluoromethoxy-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.80 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=623 [M+H]⁺

(147)1-{2-[1-(tert.-butyloxycarbonyl)-1H-indol-7-yl]-2-oxo-ethyl}-3-methyl-7-(2-butyn-1-yl)-8-bromo-xanthine

R_(f) value: 0.83 (silica gel, methylene chloride/methanol=95:5)

(148)1-[(E)-3-(2-nitro-phenyl)-2-propen-1-yl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=578 [M+H]⁺

(149)1-((E)-3-pentafluorophenyl-2-propen-1-yl)-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=623 [M+H]⁺

(150)1-[(4-nitro-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.41 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=602 [M+H]⁺

(151)1-[(benzooxazol-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.40 (silica gel, cyclohexane/ethyl acetate=3:7)

Mass spectrum (ESI⁺): m/z=548 [M+H]⁺

(152)1-[(5-nitro-benzooxazol-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.50 (silica gel, cyclohexane/ethyl acetate/methanol=5:4:1)

Mass spectrum (ESI⁺): m/z=593 [M+H]⁺

(153)1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(3-methyl-1-buten-1-yl)-8-bromo-xanthine

R_(f) value: 0.65 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=468, 470 [M+H]⁺

(154)1-[(quinolin-7-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonyl-amino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=558 [M+H]⁺

(155)1-[([1,5]naphthyridin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=559 [M+H]⁺

(156)1-[(8-methyl-quinoxalin-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.45 (silica gel, methylene chloride/methanol=19:1)

Mass spectrum (ESI⁺): m/z=573 [M+H]⁺

(157)1-[(2,3,8-trimethyl-quinoxalin-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.32 (silica gel, methylene chloride/methanol=96:4)

Mass spectrum (ESI⁺): m/z=601 [M+H]⁺

(158)1-[([1,6]naphthyridin-5-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.20 (silica gel, ethyl acetate/methanol=98:2)

Mass spectrum (ESI⁺): m/z=559 [M+H]⁺

(159)1-[([1,8]naphthyridin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.12 (silica gel, ethyl acetate/methanol=98:2)

Mass spectrum (ESI⁺): m/z=559 [M+H]⁺

(160)1-[(4-fluoro-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.47 (silica gel, petroleum ether/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=575 [M+H]⁺

(161)1-[([1,5]naphthyridin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.39 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=559 [M+H]⁺

(162)1-[2-(3-methyl-2-oxo-2,3-dihydro-benzooxazol-4-yl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.60 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=606 [M+H]⁺

(163)1-[(8-phenyl-quinoxalin-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.48 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=356 [M+H]⁺

(164)1-[([1,5]naphthyridin-4-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.25 (silica gel, ethyl acetate/petroleum ether=4:1)

Mass spectrum (ESI⁺): m/z=559 [M+H]⁺

(165)1-((E)-3-pentafluorophenyl-allyl)-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=623 [M+H]⁺

(166)1-[(E)-3-(2-trifluoromethyl-phenyl)-allyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=601 [M+H]⁺

(167)1-[(E)-3-(3-trifluoromethyl-phenyl)-allyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=601 [M+H]⁺

(168)1-[(E)-3-(4-trifluoromethyl-phenyl)-allyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=601 [M+H]⁺

(169)1-[(3-trifluoromethyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.68 (silica gel, cyclohexane/ethyl acetate=3:7)

Mass spectrum (ESI⁺): m/z=626 [M+H]⁺

(170)1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-cyano-benzyl)-8-chloro-xanthine(171)1-[(3-difluoromethyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.38 (silica gel, cyclohexane/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=608 [M+H]⁺

(172)1-[(4-chloro-3-methoxy-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.65 (silica gel, methylene chloride/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=622, 624 [M+H]⁺

(173)1-[(4-ethoxy-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.25 (silica gel, methylene chloride/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=603 [M+H]⁺

(174)1-[(4-isopropyloxy-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.40 (silica gel, methylene chloride/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=617 [M+H]⁺

(175)1-[(2-methyl-benzothiazol-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.56 (silica gel, methylene chloride/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=578 [M+H]⁺

(176)1-[(3-phenyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.75 (silica gel, methylene chloride/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=634 [M+H]⁺

(177)1-[(4-phenyloxy-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.35 (silica gel, methylene chloride/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=651 [M+H]⁺

(178)1-[(4-phenyl-quinazolin-2-yl)methyl]-3-cyclopropyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.45 (silica gel, methylene chloride/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=661 [M+H]⁺

(179)1-[(3-methyl-isoquinolin-1-yl)methyl]-3-cyclopropyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.50 (silica gel, methylene chloride/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=598 [M+H]⁺

(180)1-[2-(3-difluoromethoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.77 (silica gel, methylene chloride/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=601 [M+H]⁺

(181)1-[(2-phenyl-quinazolin-4-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.65 (silica gel, methylene chloride/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=635 [M+H]⁺

(182)1-[2-(2-methoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.57 (silica gel, methylene chloride/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=565 [M+H]⁺

(183)1-[2-(3-methoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.63 (silica gel, methylene chloride/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=565 [M+H]⁺

(184)1-[2-(3-trifluoromethoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.64 (silica gel, methylene chloride/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=619 [M+H]⁺

(185)1-[2-(biphenyl-2-yl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.70 (silica gel, methylene chloride/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=611 [M+H]⁺

(186)1-[2-(biphenyl-3-yl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.75 (silica gel, methylene chloride/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=611 [M+H]⁺

(187)1-[2-(3-isopropyloxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.66 (silica gel, methylene chloride/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=593 [M+H]⁺

(188)1-[(3-methyl-isoquinolin-1-yl)methyl]-3-cyclopropyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.50 (silica gel, methylene chloride/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=598 [M+H]⁺

(189)1-[(4-phenyl-quinazolin-2-yl)methyl]-3-cyclopropyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.50 (silica gel, methylene chloride/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=661 [M+H]⁺

(190)1-[(4-cyano-naphthalen-1-yl)methyl]-3-cyclopropyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.75 (silica gel, methylene chloride/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=608 [M+H]⁺

(191)1-[2-(2-phenyloxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.85 (silica gel, methylene chloride/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=627 [M+H]⁺

(192)1-[2-(3-ethoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.72 (silica gel, methylene chloride/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=579 [M+H]⁺

(193)1-[2-(3-methoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.67 (silica gel, methylene chloride/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=565 [M+H]⁺

(194)1-[2-(2-methoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl)-xanthine

R_(f) value: 0.57 (silica gel, methylene chloride/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=565 [M+H]⁺

(195)1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-chloro-benzyl)-8-bromo-xanthine(196)1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-bromo-benzyl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine(197)1-[(1,2,3,4-tetrahydro-phenanthridin-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.55 (silica gel, ethyl acetate/petroleum ether=2:1)

Mass spectrum (ESI⁺): m/z=612 [M+H]⁺

EXAMPLE VI1-(2-{3-[(methanesulphinyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

To a solution of 402 mg of1-(2-{3-[(methylsulphanyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthinein 10 ml hexafluoroisopropanol are added 0.15 ml of a 35% hydrogenperoxide solution. The reaction mixture is stirred for half an hour atambient temperature. Then 5 ml of a 10% sodium thiosulphate solution areadded. The aqueous phase is extracted twice with 5 ml of methylenechloride. The combined extracts are dried over sodium sulphate andevaporated down. The yellow residue is purified by chromatographythrough a silica gel column with cyclohexane/ethyl acetate/methanol(5:4:1) as eluant.

Yield: 299 mg (73% of theory)

R_(f) value: 0.28 (silica gel, cyclohexane/ethyl acetate/methanol=5:4:1)

Mass spectrum (ESI⁺): m/z=643 [M+H]⁺

The following compounds are obtained analogously to Example VI:

(1)1-[2-(3-methanesulphinyl-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.05 (silica gel, ethyl acetate/cyclohexane=3:1)

Mass spectrum (ESI⁺): m/z=613 [M+H]⁺

(2)1-(2-{2-[(methanesulphinyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=627 [M+H]⁺

EXAMPLE VII3-[(2-trimethylsilanyl-ethoxy)methyl]-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

236 μl of 1,8-diazabicyclo[5.4.0]undec-7-ene are added dropwise to 630mg of7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthinein 11 ml of acetonitrile. The solution is stirred for two hours atambient temperature, then the acetonitrile is distilled off in vacuo.The flask residue is taken up in 11 ml of N,N-dimethylformamide andcombined with 258 mg of (2-trimethylsilanyl-ethoxy)methyl chloride. Thereaction mixture is stirred for three hours at 120° C. For working upwater is added, the precipitate formed is filtered off and taken up inethyl acetate. The solution is dried over magnesium sulphate, evaporateddown and chromatographed through a silica gel column withcyclohexane/ethyl acetate/methanol (6:1:0 to 0:5:1) as eluant.

Yield: 435 mg (53% of theory)

Mass spectrum (ESI⁺): m/z=549 [M+H]⁺

The following compounds are obtained analogously to Example VII:

(1) 3-[(2-trimethylsilanyl-ethoxy)methyl]-7-(2-cyano-benzyl)-xanthine

Mass spectrum (ESI⁻): m/z=396 [M−H]⁻

(2)3-[(methoxycarbonyl)methyl]-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonyl-amino)-piperidin-1-yl]-xanthine

R_(f) value: 0.31 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=491 [M+H]⁺

EXAMPLE VIII7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

510 mg of potassium-tert. butoxide are added to 2.32 g of2-[3-(tert.-butyloxycarbonyl-amino)-piperidin-1-yl]-3-(3-methyl-2-buten-1-yl)-4-ethoxycarbonyl-5-{[(ethoxycarbonylamino)carbonyl]amino}-3H-imidazolein 35 ml of ethanol. The yellow solution is refluxed for five hours.After cooling to ambient temperature it is diluted with methylenechloride. The organic phase is washed with saturated ammonium chloridesolution and saturated sodium chloride solution, dried over magnesiumsulphate and evaporated down. The crude product is purified bychromatography through a silica gel column with methylenechloride/methanol/conc. methanolic ammonia (95:5:1 to 90:10:1) aseluant.

Yield: 630 mg (35% of theory)

R_(f) value: 0.24 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=419 [M+H]⁺

EXAMPLE IX2-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-3-(3-methyl-2-buten-1-yl)-4-ethoxycarbonyl-5-{[(ethoxycarbonylamino)carbonyl]amino}-3H-imidazole

2.97 ml of ethyl isocyanatoformate are added to 4.00 g of2-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-3-(3-methyl-2-buten-1-yl)-4-ethoxycarbonyl-5-amino-3H-imidazolein 90 ml of 1,2-dimethoxyethane and the light brown solution is heatedovernight at 120° C. in an oil bath. Then a further 0.6 ml of ethylisocyanatoformate is added and heating is continued for a further fourhours. For working up the reaction mixture is combined with saturatedpotassium carbonate solution and extracted with ethyl acetate. Theorganic phase is dried over magnesium sulphate, evaporated down andpurified through a silica gel column with methylenechloride/methanol/conc. methanolic ammonia (98:2:1 to 90:10:1) aseluant.

Yield: 2.27 g (45% of theory)

R_(f) value: 0.29 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=537 [M+H]⁺

EXAMPLE X2-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-3-(3-methyl-2-buten-1-yl)-4-ethoxycarbonyl-5-amino-3H-imidazole

Prepared by refluxingcyanimino-[N-(3-methyl-2-buten-1-yl)-N-(ethoxycarbonylmethyl)-amino]-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-methanewith sodium in ethanol.

R_(f) value: 0.26 (aluminium oxide, ethyl acetate/petroleum ether=8:2)

Mass spectrum (ESI⁺): m/z=422 [M+H]⁺

EXAMPLE XICyanimino-[N-(3-methyl-2-buten-1-yl)-N-(ethoxycarbonylmethyl)-amino]-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-methane

Prepared by reactingcyanimino-[N-(3-methyl-2-buten-1-yl)-N-(ethoxycarbonylmethyl)-amino]-phenyloxy-methanewith 3-(tert.-butyloxycarbonylamino)-piperidine in the presence ofpotassium carbonate in N,N-dimethylformamide at ambient temperature.

R_(f) value: 0.10 (silica gel, petroleum ether/ethyl acetate=6:4)

Mass spectrum (ESI⁺): m/z=422 [M+H]⁺

EXAMPLE XIIcyanimino-[N-(3-methyl-2-buten-1-yl)-N-(ethoxycarbonylmethyl)-amino]-phenyloxy-methane

Prepared by reactingcyanimino-[(ethoxycarbonylmethyl)amino]-phenyloxy-methane with1-bromo-3-methyl-2-butene in the presence of potassium carbonate inacetone at ambient temperature.

R_(f) value: 0.70 (silica gel, cyclohexane/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=316 [M+H]⁺

EXAMPLE XIII cyanimino-[(ethoxycarbonylmethyl)amino]-phenyloxy-methan

Prepared by reacting diphenylcyanocarbonimidate with ethylaminoacetate-hydrochloride in the presence of triethylamine inisopropanol at ambient temperature (analogously to R. Besse et al.,Tetrahedron 1990, 46, 7803-7812).

R_(f) value: 0.73 (silica gel, petroleum ether/ethyl acetate=8:2)

Mass spectrum (ESI⁺): m/z=248 [M+H]⁺

EXAMPLE XIV1-methyl-3-[(methoxycarbonyl)methyl]-7-(2-cyano-benzyl)-8-chloro-xanthine

Prepared by reacting 1-methyl-7-(2-cyano-benzyl)-8-chloro-xanthine withmethyl bromoacetate in the presence of potassium carbonate inN,N-dimethylformamide at ambient temperature.

R_(f) value: 0.80 (silica gel, methylene chloride/methanol=9:1)

Mass spectrum (ESI⁺): m/z=388, 390 [M+H]⁺

The following compounds are obtained analogously to Example XIV:

(1) 1-methyl-3-cyanomethyl-7-(2-cyano-benzyl)-8-chloro-xanthine

Mass spectrum (ESI⁺): m/z=355, 357 [M+H]⁺

(2) 1-methyl-3-(2-propyn-1-yl)-7-(2-cyano-benzyl)-8-chloro-xanthine

R_(f) value: 0.80 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=354, 356 [M+H]⁺

(3) 1-methyl-3-(2-propen-1-yl)-7-(2-cyano-benzyl)-8-chloro-xanthine

R_(f) value: 0.90 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=356, 358 [M+H]⁺

(4)1-(2-phenyl-2-oxo-ethyl)-3-cyanomethyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.78 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=576 [M+H]⁺

(5) 1-methyl-3-isopropyl-7-(2-cyano-benzyl)-8-chloro-xanthine

Mass spectrum (ESI⁺): m/z=358, 360 [M+H]⁺

EXAMPLE XV 1-methyl-7-(2-cyano-benzyl)-8-chloro-xanthine

Prepared by treating1-methyl-3-[(2-trimethylsilanyl-ethoxy)methyl]-7-(2-cyano-benzyl)-8-chloro-xanthinewith trifluoroacetic acid in methylene chloride at ambient temperature.

R_(f) value: 0.50 (silica gel, methylene chloride/methanol=9:1)

Mass spectrum (ESI⁺): m/z=316, 318 [M+H]⁺

The following compounds are obtained analogously to Example XV:

(1) 1-(2-phenyl-2-oxo-ethyl)-3-methyl-8-bromo-xanthine

R_(f) value: 0.26 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁻): m/z=361, 363 [M−H]⁻

(2)1-[(4-oxo-3,4-dihydro-phthalazin-1-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(As the compound still contains impurities which cannot be removed bychromatography, the material is again converted into the BOC-protectedderivative and then purified by chromatography, cf. Ex. XXV(1).)

Mass spectrum (ESI⁺): m/z=491 [M+H]⁺

EXAMPLE XVI1-methyl-3-[(2-trimethylsilanyl-ethoxy)methyl]-7-(2-cyano-benzyl)-8-chloro-xanthine

Prepared by chlorination of1-methyl-3-[(2-trimethylsilanyl-ethoxy)methyl]-7-(2-cyano-benzyl)-xanthinewith N-chlorosuccinimide in dichloroethane while refluxing.

Mass spectrum (EI): m/z=445, 447 [M]⁺

EXAMPLE XVII 7-(2-cyano-benzyl)-xanthine

Prepared by treating 16.68 g of2-amino-7-(2-cyano-benzyl)-1,7-dihydro-purin-6-one with 17.00 g ofsodium nitrite in a mixture of 375 ml of conc. acetic acid, 84 ml ofwater and 5.2 ml of conc. hydrochloric acid at 50° C.

Yield: 8.46 g (50% of theory)

Mass spectrum (ESI⁺): m/z=268 [M+H]⁺

EXAMPLE XVIII 2-amino-7-(2-cyano-benzyl)-1,7-dihydro-purin-6-one

Prepared by reacting 20.00 g of guanosine-hydrate with 22.54 g of2-cyano-benzylbromide in dimethylsulphoxide at 60° C. and subsequenttreatment with 57 ml of conc. hydrochloric acid.

Yield: 18.00 g (97% of theory)

Mass spectrum (ESI⁺): m/z=267 [M+H]⁺

EXAMPLE XIX1-{2-[3-(2-oxo-imidazolidin-1-yl)-phenyl]-2-oxo-ethyl}-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Prepared by treating1-[2-(3-{[(2-chloro-ethylamino)carbonyl]amino}-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthinewith potassium-tert. butoxide in N,N-dimethylformamide at ambienttemperature.

R_(f) value: 0.50 (silica gel, methylene chloride/methanol=9:1)

EXAMPLE XX1-[2-(3-{[(2-chloro-ethylamino)carbonyl]amino}-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Prepared by reacting 221 mg of1-[2-(3-amino-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthinewith 60 μl of 2-chloroethyl isocyanate in 3 ml methylene chloride atambient temperature.

Yield: 163 mg (64% of theory)

R_(f) value: 0.20 (silica gel, cyclohexane/ethyl acetate/methanol=6:3:1)

Mass spectrum (ESI⁺): m/z=671, 673 [M+H]⁺

The following compounds are obtained analogously to Example XX:

(1)1-[2-(2-{[(ethoxycarbonylamino)carbonyl]amino}-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(Carried out in N,N-dimethylformamide at 30° C.)

R_(f) value: 0.26 (silica gel, cyclohexane/ethyl acetate=4:6)

Mass spectrum (ESI⁺): m/z=681 [M+H]⁺

EXAMPLE XXI1-[2-(3-amino-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Prepared by treating1-[2-(3-nitro-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthinewith iron powder in a mixture of ethanol, water and glacial acetic acid(80:25:10) at 100° C.

R_(f) value: 0.55 (silica gel, cyclohexane/ethyl acetate/methanol/conc.aqueous ammonia=50:30:20:1)

Mass spectrum (ESI⁺): m/z=566 [M+H]⁺

The following compounds are obtained analogously to Example XXI:

(1)1-[2-(2-amino-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=566 [M+H]⁺

(2)1-[2-(2-amino-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=566 [M+H]⁺

(3)1-[(5-amino-isoquinolin-1-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.22 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=589 [M+H]⁺

(4)1-[2-(2-amino-phenyl)-2-oxo-ethyl]-3-methyl-7-[(1-cyclopenten-1-yl)methyl]-8-bromo-xanthine

Mass spectrum (ESI⁺): m/z=458, 460 [M+H]⁺

(5)1-[2-(2-amino-phenyl)-2-oxo-ethyl]-3-methyl-7-((E)-2-buten-1-yl)-8-bromo-xanthine

(product contains approx. 10% of Z isomer)

R_(f) value: 0.55 (silica gel, cyclohexane/ethyl acetate=4:6)

Mass spectrum (ESI⁺): m/z=432, 434 [M+H]⁺

(6)1-[2-(2-amino-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-bromo-xanthine

R_(f) value: 0.50 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=430, 432 [M+H]⁺

(7)1-[2-(2-amino-phenyl)-2-oxo-ethyl]-3-methyl-7-((E)-2-buten-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=552 [M+H]⁺

(8)1-[2-(2-amino-phenyl)-2-oxo-ethyl]-3-methyl-7-((E)-2-buten-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=552 [M+H]⁺

(9)1-[2-(2-amino-3-methoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.82 (silica gel, ethyl acetate/petroleum ether=4:1)

Mass spectrum (ESI⁺): m/z=596 [M+H]⁺

EXAMPLE XXII1-(2-{2-[(ethylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Prepared by reacting 248 mg of1-[2-(2-amino-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthinewith 40 μl of propionic acid chloride in the presence of 60 μl ofpyridine in N,N-dimethylformamide at 80° C.

Yield: 168 mg (62% of theory)

R_(f) value: 0.55 (silica gel, cyclohexane/ethyl acetate=3:7)

Mass spectrum (ESI⁺): m/z=622 [M+H]⁺

The following compounds are obtained analogously to Example XXII:

(1)1-({5-[(methoxycarbonyl)methylamino]-isoquinolin-1-yl}methyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(Carried out with methyl bromoacetate and potassium carbonate)

R_(f) value: 0.42 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=661 [M+H]⁺

(2)1-[2-(2-acetylamino-phenyl)-2-oxo-ethyl]-3-methyl-7-((E)-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(product contains approx. 10% of Z isomer)

Mass spectrum (ESI⁺): m/z=594 [M+H]⁺

(3)1-(2-{2-[(isopropylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(product contains approx. 10% of Z isomer)

Mass spectrum (ESI⁺): m/z=622 [M+H]⁺

(4)1-[2-(2-acetylamino-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.50 (silica gel, cyclohexane/ethyl acetate=3:7)

Mass spectrum (ESI⁺): m/z=608 [M+H]⁺

(5)1-[2-(2-acetylamino-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.34 (silica gel, cyclohexane/ethyl acetate=3:7)

Mass spectrum (ESI⁺): m/z=592 [M+H]⁺

(6)1-(2-{2-[(isopropylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.25 (silica gel, cyclohexane/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=636 [M+H]⁺

(7)1-(2-{2-[(isopropylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.44 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=620 [M+H]⁺

(8)1-[2-(2-acetylamino-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.34 (silica gel, cyclohexane/ethyl acetate=3:7)

Mass spectrum (ESI⁺): m/z=592 [M+H]⁺

(9)1-(2-{2-[(isopropylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.44 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=620 [M+H]⁺

(10)1-(2-{2-[(methoxycarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(Carried out in acetonitrile at 55° C.)

R_(f) value: 0.25 (silica gel, cyclohexane/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=624 [M+H]⁺

(11)1-(2-{2-[(isopropylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(Carried out in acetonitrile at 65° C.)

R_(f) value: 0.50 (silica gel, cyclohexane/ethylacetate/isopropanol=14:3:3)

Mass spectrum (ESI⁺): m/z=622 [M+H]⁺

(12)1-(2-{2-[(ethylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=608 [M+H]⁺

(13)1-[2-(2-acetylamino-phenyl)-2-oxo-ethyl]-3-methyl-7-((E)-2-buten-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=594 [M+H]⁺

(14)1-[2-(2-acetylamino-phenyl)-2-oxo-ethyl]-3-methyl-7-((E)-2-buten-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.28 (silica gel, cyclohexane/ethylacetate/isopropanol=8:1:1)

Mass spectrum (ESI⁺): m/z=594 [M+H]⁺

(15)1-(2-{2-[(isopropylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.90 (silica gel, methylene chloride/methanol=9:1)

(16)1-(2-{2-[(isopropylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl])-xanthine

(Carried out in 1,2-dichloroethane at 45° C.)

R_(f) value: 0.30 (silica gel, cyclohexane/ethylacetate/isopropanol=8:1:1)

Mass spectrum (ESI⁺): m/z=622 [M+H]⁺

(17)1-(2-{2-[(ethylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.48 (silica gel, cyclohexane/ethylacetate/isopropanol=14:3:3)

Mass spectrum (ESI⁺): m/z=608 [M+H]⁺

(18)1-(2-{2-[(ethylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=606 [M+H]⁺

(19)1-(2-{2-[(ethylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.22 (silica gel, methylene chloride/methanol=95:5)

(20)1-(2-{2-[(phenylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.55 (silica gel, cyclohexane/ethylacetate/isopropanol=14:3:3)

Mass spectrum (ESI⁺): m/z=656 [M+H]⁺

(21)1-(2-{2-[(cyclopropylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-[(1-cyclopenten-1-yl)methyl]-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(Carried out with Hünig base and 4-dimethylamino-pyridine in methylenechloride)

R_(f) value: 0.60 (silica gel, methylene chloride/methanol=18:1)

EXAMPLE XXIII1-(2-{3-[(methoxycarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

Prepared by treating1-(2-{3-[(methoxycarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthinewith trifluoroacetic acid in methylene chloride at ambient temperature.

Mass spectrum (ESI⁺): m/z=539 [M+H]⁺

The following compounds are obtained analogously to Example XXIII:

(1)1-(2-{2-[(methoxycarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=539 [M+H]⁺

EXAMPLE XXIV 1-methyl-3-phenyl-7-(2-cyano-benzyl)-8-chloro-xanthine

A mixture of 829 mg of 1-methyl-7-(2-cyano-benzyl)-8-chloro-xanthine,640 mg of phenylboric acid, 509 mg of anhydrous copper acetate and 0.43ml of pyridine in 20 ml methylene chloride is stirred for four days atambient temperature in the presence of 100 mg of 4 Å molecular sieves.Then another 320 mg of phenylboric acid are added and the reactionmixture is stirred for another day at ambient temperature. For workingup the mixture is filtered through talc and washed with ethyl acetate.The filtrate is evaporated down and chromatographed through a silica gelcolumn with cyclohexane/ethyl acetate (7:3 to 1:1) as eluant.

Yield: 142 mg (14% of theory)

Mass spectrum (ESI⁺): m/z=392, 394 [M+H]⁺

EXAMPLE XXV1-(2-phenyl-2-oxo-ethyl)-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonyl-amino)-piperidin-1-yl]-xanthine

Prepared by reacting1-(2-phenyl-2-oxo-ethyl)-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthinewith di-tert.butyl pyrocarbonate in the presence of Hünig base inmethylene chloride at ambient temperature.

R_(f) value: 0.27 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

The following compounds are obtained analogously to Example XXV:

(1)1-[(4-oxo-3,4-dihydro-phthalazin-1-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonyl-amino)-piperidin-1-yl]-xanthine

R_(f) value: 0.27 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=591 [M+H]⁺

(2) 7-acetyl-1-(tert.-butyloxycarbonyl)-1H-indole

R_(f) value: 0.82 (silica gel, methylene chloride/petroleum ether/ethylacetate=5:4:1)

Mass spectrum (ESI⁺): m/z=260 [M+H]⁺

EXAMPLE XXVI1-[(cinnolin-4-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthineand1-[(1,4-dihydro-cinnolin-4-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine

510 mg of a mixture of (cinnolin-4-yl)-methanol and(1,4-dihydro-cinnolin-4-yl)-methanol (see Ex. XXVII) are added to 830 mgof 3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine and 1.25 g oftriphenylphosphine in 25 ml of tetrahydrofuran. The reaction mixture iscombined with 0.92 ml diethyl azodicarboxylate and stirred overnight atambient temperature. Then it is evaporated down and chromatographedthrough a silica gel column with ethyl acetate/petroleum ether (7:3 to0:1) as eluant. A mixture of cinnoline and 1,4-dihydro-cinnolinecompound is obtained.

Yield: 660 mg (52% of theory)

R_(f) value: 0.60 (silica gel, ethyl acetate/petroleum ether=7:3)

The following compounds are obtained analogously to Example XXVI:

(1)1-({4-oxo-3-[(2-trimethylsilanyl-ethoxy)methyl]-3,4-dihydro-phthalazin-1-yl}methyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine

R_(f) value: 0.85 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=557, 559 [M+H]⁺

(2)1-[(isoquinolin-3-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine

Melting point: 194-195° C.

Mass spectrum (ESI⁺): m/z=410, 412 [M+H]⁺

(3)1-[(3-methyl-4-oxo-3,4-dihydro-phthalazin-1-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-chloro-xanthine

R_(f) value: 0.66 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=441, 443 [M+H]⁺

(4) 1-[(quinolin-4-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-bromo-xanthine

(Carried out with potassium carbonate)

R_(f) value: 0.45 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=438, 440 [M+H]⁺

(5)1-[(isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-bromo-xanthine

R_(f) value: 0.78 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=438, 440 [M+H]⁺

(6)1-[(4-dimethylamino-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.80 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=600 [M+H]⁺

(7)1-[(isoquinolin-1-yl)methyl]-3-methyl-7-((E)-2-buten-1-yl)-8-bromo-xanthine

(The product contains approx. 20% of Z isomer)

R_(f) value: 0.71 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=440, 442 [M+H]⁺

(8)1-[(1-methyl-1H-indol-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-bromo-xanthine

R_(f) value: 0.95 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=440, 442 [M+H]⁺

(9) 1-[(quinolin-3-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-bromo-xanthine

R_(f) value: 0.55 (silica gel, ethyl acetate/petroleum ether=8:2)

Mass spectrum (ESI⁺): m/z=438, 440 [M+H]⁺

(10)1-{[1-(tert.-butyloxycarbonylamino)-1H-indol-2-yl]methyl}-3-methyl-7-(2-butyn-1-yl)-8-bromo-xanthine

R_(f) value: 0.74 (silica gel, petroleum ether/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=526, 528 [M+H]⁺

(11)1-({2-methyl-1-[(2-trimethylsilanyl-ethoxy)methyl]-1H-benzoimidazol-5-yl}methyl)-3-methyl-7-(2-butyn-1-yl)-8-bromo-xanthine(mixed with1-({2-methyl-3-[(2-trimethylsilanyl-ethoxy)methyl]-3H-benzoimidazol-5-yl}methyl)-3-methyl-7-(2-butyn-1-yl)-8-bromo-xanthine)

Mass spectrum (ESI⁺): m/z=571, 573 [M+H]⁺

(12)1-[(1-[(2-trimethylsilanyl-ethoxy)methyl]-1H-benzoimidazol-5-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-bromo-xanthine(mixed with1-[(3-[(2-trimethylsilanyl-ethoxy)methyl]-3H-benzoimidazol-5-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-bromo-xanthine)

R_(f) value: 0.50 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=557, 559 [M+H]⁺

(13)1-[(pyrazolo[1,5-a]pyridin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-bromo-xanthine

R_(f) value: 0.35 (silica gel, petroleum ether/ethyl acetate=1:2)

Mass spectrum (ESI⁺): m/z=427, 429 [M+H]⁺

EXAMPLE XXVII (cinnolin-4-yl)-methanol and(1,4-dihydro-cinnolin-4-yl)-methanol

A solution of 1.00 g of methyl cinnolin-4-carboxylate in 15 ml diethylether is added dropwise at 0° C. to a suspension of 222 mg of lithiumaluminium hydride in 5 ml of diethyl ether. After 1.5 hours water iscarefully added dropwise to the reaction mixture, this is stirred withmethylene chloride and suction filtered through a glass fibre filter.The aqueous phase is extracted with methylene chloride and the combinedorganic phases are dried over magnesium sulphate and evaporated down.According to ¹H-NMR a mixture of cinnoline and 1,4-dihydro-cinnolinecompound is obtained as a yellow oil which is reacted further withoutany more purification.

Yield: 530 mg (62% of theory)

R_(f) value: 0.63 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=161 [M1+H]⁺ and 163 [M2+H]⁺

The following compounds are obtained analogously to Example XXVII:

(1){2-methyl-1-[(2-trimethylsilanyl-ethoxy)methyl]-1H-benzoimidazol-5-yl}-methanol

(mixed with{2-methyl-3-[(2-trimethylsilanyl-ethoxy)methyl]-3H-benzoimidazol-5-yl}-methanol)

Mass spectrum (ESI⁺): m/z=293 [M+H]⁺

(2) (2,3,8-trimethyl-quinoxalin-6-yl)-methanol

R_(f) value: 0.45 (silica gel, petroleum ether/ethyl acetate=1:2)

Mass spectrum (ESI⁺): m/z=203 [M+H]⁺

(3) (8-methyl-quinoxalin-6-yl)-methanol

R_(f) value: 0.18 (silica gel, cyclohexane/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=175 [M+H]⁺

(4) (E)-3-pentafluorophenyl-2-propen-1-ol

(Carried out with diisobutylaluminium hydride in toluene)

Mass spectrum (EI): m/z=224 [M]⁺

(5) (E)-3-(2-trifluoromethyl-phenyl)-2-propen-1-ol

(Carried out with diisobutylaluminium hydride in toluene)

(6) (E)-3-(3-trifluoromethyl-phenyl)-2-propen-1-ol

(Carried out with diisobutylaluminium hydride in toluene)

Mass spectrum (EI): m/z=202 [M]⁺

(7) (E)-3-(4-trifluoromethyl-phenyl)-2-propen-1-ol

(Carried out with diisobutylaluminium hydride in toluene)

EXAMPLE XXVIII4-hydroxymethyl-2-[(2-trimethylsilanyl-ethoxy)methyl]-2H-phthalazin-1-one

Prepared by treating methyl4-oxo-3-[(2-trimethylsilanyl-ethoxy)methyl]-3,4-dihydro-phthalazin-1-carboxylatewith sodium borohydride in tetrahydrofuran at 40° C.

R_(f) value: 0.55 (silica gel, cyclohexane/ethyl acetate 1:1)

Mass spectrum (ESI⁺): m/z=307 [M+H]⁺

The following compounds are obtained analogously to Example XXVIII:

(1) (3,4-dimethyl-isoquinolin-1-yl)-methanol

(Carried out with lithium borohydride in tetrahydrofuran)

R_(f) value: 0.35 (silica gel, petroleum ether/ethyl acetate=2:1)

Mass spectrum (ESI⁺): m/z=188 [M+H]⁺

(2) (3-methyl-imidazo[1,2-a]pyridin-2-yl)-methanol

(Carried out with lithium borohydride in tetrahydrofuran)

R_(f) value: 0.48 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=163 [M+H]⁺

(3) (3,4-dimethyl-6,7-dihydro-5H-[2]pyrindin-1-yl)-methanol

(Carried out with lithium borohydride in tetrahydrofuran)

R_(f) value: 0.40 (aluminium oxide, petroleum ether/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=178 [M+H]⁺

(4) (3,4-dimethyl-5,6,7,8-tetrahydro-isoquinolin-1-yl)-methanol

(Carried out with lithium borohydride in tetrahydrofuran)

R_(f) value: 0.45 (aluminium oxide, petroleum ether/ethyl acetate=3:1)

Mass spectrum (ESI⁺): m/z=192 [M+H]⁺

(5) 6-hydroxymethyl-1,2,3,4-tetrahydro-phenanthridine

(Carried out with lithium borohydride in tetrahydrofuran at ambienttemperature)

R_(f) value: 0.40 (silica gel, petroleum ether/ethyl acetate=2:1)

Mass spectrum (ESI⁺): m/z=214 [M+H]⁺

EXAMPLE XXIX Methyl4-oxo-3-[(2-trimethylsilanyl-ethoxy)methyl]-3,4-dihydro-phthalazin-1-carboxylate

Prepared by reacting methyl 4-oxo-3,4-dihydro-phthalazin-1-carboxylatewith (2-trimethylsilanyl-ethoxy)methylchloride in the presence of Hünigbase in methylene chloride at ambient temperature.

R_(f) value: 0.75 (silica gel, cyclohexane/ethyl acetate 6:4)

Mass spectrum (ESI⁺): m/z=335 [M+H]⁺

The following compounds are obtained analogously to Example XXIX:

(1) 7-acetyl-3-[(2-trimethylsilanyl-ethoxy)methyl]-3H-benzooxazol-2-one

Mass spectrum (ESI⁺): m/z=308 [M+H]⁺

(2) 4-acetyl-3-[(2-trimethylsilanyl-ethoxy)methyl]-3H-benzooxazol-2-one

R_(f) value: 0.87 (silica gel, methylene chloride/methanol=99:1)

(3)4-acetyl-1,3-bis-[(2-trimethylsilanyl-ethoxy)methyl]-1,3-dihydro-benzoimidazol-2-one

(Carried out with potassium-tert. butoxide in N,N-dimethylformamide)

R_(f) value: 0.90 (silica gel, petroleum ether/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=437 [M+H]⁺

(4) 6-methyl-1-[(2-trimethylsilanyl-ethoxy)methyl]-1H-quinolin-2-one

R_(f) value: 0.78 (silica gel, petroleum ether/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=290 [M+H]⁺

(5) methyl{2-methyl-1-[(2-trimethylsilanyl-ethoxy)methyl]-1H-benzoimidazol-5-yl}-carboxylate(mixed with methyl{2-methyl-3-[(2-trimethylsilanyl-ethoxy)methyl]-3H-benzoimidazol-5-yl}-carboxylate)

Mass spectrum (ESI⁺): m/z=321 [M+H]⁺

EXAMPLE XXX1-[2-(3-methanesulphonyl-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

0.22 ml of a 35% hydrogen peroxide solution and 20 mg of sodiumtungstate are added to 500 mg of1-[2-(3-methylsulphanyl-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthinein 5 ml methylene chloride. The reaction mixture is stirred overnight atambient temperature, then 1 ml of methanol is added. After another 48hours a further 1.5 ml of 35% hydrogen peroxide solution, a spatula tipof sodium tungstate and two drops of water are added. The next morning,the oxidation is complete according to thin layer chromatography and thereaction mixture is diluted with 50 ml methylene chloride and washedtwice with 30 ml of 10% sodium thiosulphate solution. The organic phaseis dried over magnesium sulphate and evaporated down, leaving a viscousresin which is reacted further without any more purification.

Yield: 530 mg (100% of theory)

R_(f) value: 0.72 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=629 [M+H]⁺

EXAMPLE XXXI1-[2-(3-carboxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Prepared by treating1-[2-(3-methoxycarbonyl-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthinewith 3 M sodium hydroxide solution in methanol at ambient temperature.

R_(f) value: 0.34 (silica gel, methylene chloride/methanol=9:1)

Mass spectrum (ESI⁺): m/z=595 [M+H]⁺

The following compounds are obtained analogously to Example XXXI:

(1)1-[2-(2-carboxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.49 (silica gel, methylene chloride/methanol=9:1)

(2)1-[2-(2-carboxymethoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(Carried out with 4 M potassium hydroxide solution in tetrahydrofuran)

Mass spectrum (ESI⁺): m/z=609 [M+H]⁺

(3)1-[2-(2-carboxymethylamino-phenyl)-2-oxo-ethyl]-3-methyl-7-((E)-2-buten-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(Carried out with 4 M potassium hydroxide solution in tetrahydrofuran)

R_(f) value: 0.65 (silica gel, cyclohexane/ethyl acetate=3:7)

Mass spectrum (ESI⁺): m/z=610 [M+H]⁺

(4)1-carboxymethyl-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=475 [M+H]⁺

EXAMPLE XXXII1-{2-[3-(methylaminocarbonyl)-phenyl]-2-oxo-ethyl}-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

A mixture of 190 mg of1-[2-(3-carboxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine,43 μl of a 40% aqueous methylamine solution, 103 mg ofO-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate, 43mg of N-hydroxybenzotriazole and 45 μl of triethylamine in 3 ml oftetrahydrofuran is stirred for eight hours at ambient temperature. Forworking up the reaction mixture is diluted with ethyl acetate and washedwith water, 10% citric acid solution, 10% potassium carbonate solutionand saturated sodium chloride solution. The organic phase is evaporateddown and chromatographed through a silica gel column with methylenechloride/methanol (98:2 to 80:20) as eluant.

Yield: 173 mg (89% of theory)

R_(f) value: 0.30 (silica gel, methylene chloride/methanol=20:1)

Mass spectrum (ESI⁺): m/z=608 [M+H]⁺

The following compounds are obtained analogously to Example XXXII:

(1)1-{2-[3-(dimethylaminocarbonyl)-phenyl]-2-oxo-ethyl}-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.28 (silica gel, methylene chloride/methanol=20:1)

Mass spectrum (ESI⁺): m/z=622 [M+H]⁺

(2)1-{2-[3-(morpholin-4-yl-carbonyl)-phenyl]-2-oxo-ethyl}-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.30 (silica gel, methylene chloride/methanol=20:1)

Mass spectrum (ESI⁺): m/z=664 [M+H]⁺

(3)1-{2-[2-(dimethylaminocarbonyl)-phenyl]-2-oxo-ethyl}-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.30 (silica gel, methylene chloride/methanol=20:1)

Mass spectrum (ESI⁺): m/z=622 [M+H]⁺

(4)1-{2-[2-(morpholin-4-yl-carbonyl)-phenyl]-2-oxo-ethyl}-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.30 (silica gel, methylene chloride/methanol=20:1)

Mass spectrum (ESI⁺): m/z=664 [M+H]⁺

(5)1-(2-{2-[(isopropylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(Carried out with Hünig base in N,N-dimethylformamide)

Mass spectrum (ESI⁺): m/z=650 [M+H]⁺

(6)1-(2-{2-[(ethylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(Carried out with Hünig base in N,N-dimethylformamide)

Mass spectrum (ESI⁺): m/z=636 [M+H]⁺

(7)1-(2-{2-[2-oxo-2-(pyrrolidin-1-yl)-ethoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(Carried out with Hünig base in N,N-dimethylformamide)

Mass spectrum (ESI⁺): m/z=662 [M+H]⁺

(8)1-(2-{2-[2-(morpholin-4-yl)-2-oxo-ethoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

(Carried out with Hünig base in N,N-dimethylformamide)

Mass spectrum (ESI⁺): m/z=678 [M+H]⁺

(9)1-(2-{2-[(methylaminocarbonyl)methylamino]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.40 (silica gel, cyclohexane/ethyl acetate/methanol=5:4:1)

Mass spectrum (ESI⁺): m/z=623 [M+H]⁺

(10)1-[(2-amino-phenylaminocarbonyl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.40 (silica gel, cyclohexane/ethyl acetate/methanol=5:4:1)

Mass spectrum (ESI⁺): m/z=565 [M+H]⁺

EXAMPLE XXXIII 1-chloromethyl-4-methyl-isoquinoline-hydrochloride

Prepared by treating (4-methyl-isoquinolin-1-yl)-methanol with thionylchloride in methylene chloride.

R_(f) value: 0.76 (silica gel, methylene chloride/methanol/conc. aqueousammonia=95:5:0.1)

Mass spectrum (ESI⁺): m/z=192, 194 [M+H]⁺

The following compounds are obtained analogously to Example XXXIII:

(1) 1-chloromethyl-3,4-dimethyl-isoquinoline-hydrochloride

R_(f) value: 0.65 (silica gel, petroleum ether/ethyl acetate=2:1)

Mass spectrum (ESI⁺): m/z=206, 208 [M+H]⁺

(2) 5-chloromethyl-8-methoxy-quinoline-hydrochloride

Mass spectrum (ESI⁺): m/z=208, 210 [M+H]⁺

(3) 8-chloromethyl-5-methoxy-quinoline-hydrochloride

Mass spectrum (EI): m/z=207, 209 [M]⁺

(4) 2-chloromethyl-3-methyl-imidazo[1,2-a]pyridine-hydrochloride

R_(f) value: 0.55 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=181, 183 [M+H]⁺

(5) 8-chloromethyl-5-methoxy-isoquinoline-hydrochloride

Mass spectrum (ESI⁺): m/z=208, 210 [M+H]⁺

(6) 1-chloromethyl-3,4-dimethyl-6,7-dihydro-5H-[2]pyridine-hydrochloride

R_(f) value: 0.50 (aluminium oxide, petroleum ether/ethyl acetate=10:1)

Mass spectrum (ESI⁺): m/z=196, 198 [M+H]⁺

(7)1-chloromethyl-3,4-dimethyl-5,6,7,8-tetrahydro-isoquinoline-hydrochloride

R_(f) value: 0.50 (aluminium oxide, petroleum ether/ethyl acetate=10:1)

Mass spectrum (ESI⁺): m/z=210, 212 [M+H]⁺

(8) 6-chloromethyl-2,3,8-trimethyl-quinoxaline-hydrochloride

Mass spectrum (ESI⁺): m/z=221, 223 [M+H]⁺

(9) 6-chloromethyl-8-methyl-quinoxaline-hydrochloride

Mass spectrum (ESI⁺): m/z=193, 195 [M+H]⁺

(10) 6-chloromethyl-1,2,3,4-tetrahydro-phenanthridine-hydrochloride

R_(f) value: 0.50 (silica gel, petroleum ether/ethyl acetate=5:1)

Mass spectrum (ESI⁺): m/z=232, 234 [M+H]⁺

EXAMPLE XXXIV1-[(4-oxo-3,4-dihydro-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

0.5 ml of a 1 M sodium methoxide solution in methanol is added dropwiseto a solution of 428 mg of1-cyanomethyl-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthinein 3 ml of methanol at ambient temperature. After about 20 minutes thethick suspension formed is heated gently in a water bath and dilutedwith 2 ml of methanol. As soon as the reaction to form the iminoester iscomplete according to thin layer chromatography, the reaction mixture isneutralised with 0.5 ml 1 M glacial acetic acid solution in methanol andcombined with a solution of 130 mg of anthranilic acid in 2 ml ofmethanol. Gentle heating produces a clear solution, which is stirred for2.5 hours at ambient temperature. Then the reaction mixture is gentlyrefluxed for about 3.5 hours. After standing overnight at ambienttemperature the methanol is distilled off and the residue is stirredwith cold water, suction filtered and dried. The crude product issuspended in 5 ml of methanol, gently heated and after cooling suctionfiltered, washed with methanol and dried in the desiccator.

Yield: 302 mg (56% of theory)

R_(f) value: 0.55 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=575 [M+H]⁺

The following compounds are obtained analogously to Example XXXV:

(1) (4-difluoromethoxy-naphthalen-1-yl)-methanol

R_(f) value: 0.33 (silica gel, cyclohexane/ethyl acetate=6:4)

Mass spectrum (ESI⁻): m/z=223 [M−H]⁻

EXAMPLE XXXV (4-dimethylamino-naphthalen-1-yl)-methanol

prepared by reduction of 4-dimethylamino-naphthalene-1-carbaldehyde withsodium borohydride in aqueous tetrahydrofuran.

R_(f) value: 0.67 (silica gel, cyclohexane/ethyl acetate=1:1)

EXAMPLE XXXVI 2-bromo-1-(2,3-dihydro-benzo[1,4]dioxin-5-yl)-ethanone

prepared by bromination of1-(2,3-dihydro-benzo[1,4]dioxin-5-yl)-ethanone in methylene chloridewhile cooling gently with an ice bath. The dibromo compound formed as aby-product is separated off by column chromatography.

Mass spectrum (ESI⁺): m/z=257, 259 [M+H]⁺

R_(f) value: 0.92 (silica gel, methylene chloride)

The following compounds are obtained analogously to Example XXXVI:

(1) 7-(2-bromo-acetyl)-3-methyl-3H-benzooxazol-2-one

(bromination is carried out in dioxane at 40° C.; the product iscontaminated with approx. 20% dibromo compound)

R_(f) value: 0.44 (silica gel, petroleum ether/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=270, 272 [M+H]⁺

(2) 1-benzo[1,3]dioxol-4-yl-2-bromo-ethanone

Mass spectrum (ESI⁺): m/z=243, 245 [M+H]⁺

R_(f) value: 0.94 (silica gel, methylene chloride)

(3) 2-[2-(2-bromo-acetyl)-phenoxy]-N-ethyl-acetamide

(bromination is carried out with copper(II) bromide in dioxane)

Mass spectrum (ESI⁺): m/z=300, 302 [M+H]⁺

(4) 4-(2-bromo-acetyl)-3-methyl-3H-benzooxazol-2-one

R_(f) value: 0.67 (silica gel, methylene chloride/methanol=99:1)

Mass spectrum (ESI⁺): m/z=270, 272 [M+H]⁺

(5) 2-[2-(2-bromo-acetyl)-phenoxy]-N-methyl-acetamide

Mass spectrum (ESI⁺): m/z=386, 388 [M+H]⁺

(6)7-(2-bromo-acetyl)-3-[(2-trimethylsilanyl-ethoxy)methyl]-3H-benzooxazol-2-one

R_(f) value: 0.84 (silica gel, methylene chloride/methanol=99:1)

Mass spectrum (ESI⁺): m/z=384, 386 [M+H]⁺

(7) 4-(2-bromo-acetyl)-1,3-dimethyl-1,3-dihydro-benzoimidazol-2-one

R_(f) value: 0.38 (silica gel, ethyl acetate/petroleum ether=1:1)

Mass spectrum (ESI⁺): m/z=283, 285 [M+H]⁺

(8)4-(2-bromo-acetyl)-3-[(2-trimethylsilanyl-ethoxy)methyl]-3H-benzooxazol-2-one

R_(f) value: 0.82 (silica gel, methylene chloride/methanol=99:1)

(9)4-(2-bromo-acetyl)-1-ethoxycarbonyl-3-methyl-1,3-dihydro-benzoimidazol-2-one

R_(f) value: 0.39 (silica gel, petroleum ether/ethyl acetate=2:1)

Mass spectrum (ESI⁺): m/z=341, 343 [M+H]⁺

(10) 2-bromo-1-(2,2-difluoro-benzo[1,3]dioxol-4-yl)-ethanone

Mass spectrum (ESI⁻): m/z=277, 279 [M−H]⁻

EXAMPLE XXXVII (2,3-dihydro-benzo[1,4]dioxin-5-yl)-ethanone

Prepared by reacting 1-(2,3-dihydroxy-phenyl)-ethanone with1,2-dibromoethane in the presence of potassium carbonate inN,N-dimethylformamide at 100° C.

R_(f) value: 0.43 (silica gel, ethyl acetate/petroleum ether=1:4)

Mass spectrum (ESI⁺): m/z=179 [M+H]⁺

EXAMPLE XXXVIII1-[(3-methyl-4-oxo-3,4-dihydro-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Prepared by reacting1-[(4-oxo-3,4-dihydro-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthinewith methyl iodide in the presence of potassium carbonate inN,N-dimethylformamide at ambient temperature.

R_(f) value: 0.50 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=589 [M+H]⁺

The following compounds are obtained analogously to Example XXXVIII:

(1) 7-acetyl-3-methyl-3H-benzooxazol-2-one

(The methylation is carried out in the presence of sodium carbonate inmethanol)

R_(f) value: 0.46 (silica gel, petroleum ether/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=192 [M+H]⁺

(2) 4-acetyl-3-methyl-3H-benzooxazol-2-one

(The methylation is carried out in the presence of sodium carbonate inmethanol while refluxing)

R_(f) value: 0.67 (silica gel, methylene chloride/methanol=99:1)

Mass spectrum (ESI⁺): m/z=192 [M+H]⁺

(3) 4-acetyl-1,3-dimethyl-1,3-dihydro-benzoimidazol-2-one

(Carried out in the presence of potassium-tert. butoxide)

R_(f) value: 0.40 (silica gel, ethyl acetate/petroleum ether=2:1)

Mass spectrum (ESI⁺): m/z=205 [M+H]⁺

(4) 4-acetyl-1-ethoxycarbonyl-3-methyl-1,3-dihydro-benzoimidazol-2-one

R_(f) value: 0.23 (silica gel, petroleum ether/ethyl acetate=2:1)

Mass spectrum (ESI⁺): m/z=263 [M+H]⁺

(5)1-[(1-methyl-1H-benzoimidazol-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Mass spectrum (ESI⁺): m/z=561 [M+H]⁺

(6)1-{[1-(2-cyano-ethyl)-1H-benzoimidazol-2-yl]methyl}-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.50 (silica gel, cyclohexane/ethyl acetate/methanol=5:4:1)

Mass spectrum (ESI⁺): m/z=600 [M+H]⁺

(7)1-({1-[(methylaminocarbonyl)methyl]-1H-benzoimidazol-2-yl}methyl)-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.45 (silica gel, cyclohexane/ethyl acetate/methanol=5:4:1)

Mass spectrum (ESI⁺): m/z=618 [M+H]⁺

(8)1-[(1-benzyl-1H-benzoimidazol-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.50 (silica gel, cyclohexane/ethyl acetate/methanol=5:4:1)

Mass spectrum (ESI⁺): m/z=637 [M+H]⁺

EXAMPLE XXXIX1-[2-(2-cyanomethylamino-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Prepared by reacting1-[2-(2-amino-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthinewith paraformaldehyde and potassium cyanide in the presence of zincchloride in glacial acetic acid at 40° C.

R_(f) value: 0.45 (silica gel, cyclohexane/ethyl acetate=3:7)

Mass spectrum (ESI⁺): m/z=605 [M+H]⁺

EXAMPLE XL1-[2-(2-amino-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

prepared by reduction of1-[2-(2-nitro-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-[(S)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthinewith sodium dithionite in a mixture of methylglycol and water (2:1) at100° C.

R_(f) value: 0.34 (silica gel, methylene chloride/methanol=95:5)

The following compounds are obtained analogously to Example XL:

(1)1-[2-(2-amino-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

R_(f) value: 0.50 (silica gel, cyclohexane/ethyl acetate=4:6)

EXAMPLE XLI 2-chloromethyl-4-methyl-quinazoline

prepared by treatment of 2.95 g of2-chloromethyl-4-methyl-quinazoline-3-oxide with 6 ml phosphorustrichloride in 150 ml chloroform while refluxing.

Yield: 1.75 g (57% of theory)

R_(f) value: 0.81 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=193, 195 [M+H]⁺

EXAMPLE XLII 2-chloromethyl-4-dimethylamino-quinazoline

A freshly prepared solution of 202 mg of dimethylamine in 3.2 ml oftetrahydrofuran is added dropwise to 500 mg of4-chloro-2-chloromethyl-quinazoline in 5 ml of tetrahydrofuran whilecooling with an ice bath. Then the reaction mixture is stirred foranother 3.5 hours while cooling with an ice bath and then for a further30 minutes at ambient temperature.

The solvent is then gently distilled off using a rotary evaporator andthe residue is taken up in methylene chloride. The solution is washedwith saturated sodium hydrogen carbonate solution and with water, driedover magnesium sulphate and evaporated down. The solid residue isstirred with a little tert.-butylmethylether, suction filtered, washedwith petroleum ether and dried in vacuo.

Yield: 323 mg (62% of theory)

R_(f) value: 0.60 (silica gel, cyclohexane/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=222, 224 [M+H]⁺

The following compounds are obtained analogously to Example XLII:

(1) 2-chloromethyl-4-(morpholine-4-yl)-quinazoline

R_(f) value: 0.50 (silica gel, cyclohexane/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=264, 266 [M+H]⁺

(2) 2-chloromethyl-4-(piperidin-1-yl)-quinazoline

R_(f) value: 0.70 (silica gel, cyclohexane/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=262, 264 [M+H]⁺

(3)4-[4-(tert.-butyloxycarbonyl)-piperazin-1-yl]-2-chloromethyl-quinazoline

R_(f) value: 0.57 (silica gel, cyclohexane/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=363, 365 [M+H]⁺

(4) 2-chloromethyl-4-(pyrrolidin-1-yl)-quinazoline

R_(f) value: 0.50 (silica gel, cyclohexane/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=248, 250 [M+H]⁺

(5) 2-chloromethyl-4-ethoxy-quinazoline

(The reaction is carried out with sodium ethoxide in ethanol at ambienttemperature.)

R_(f) value: 0.50 (silica gel, cyclohexane/ethyl acetate=3:1)

Mass spectrum (ESI⁺): m/z=223, 225 [M+H]⁺

(6) 2-chloromethyl-4-isopropyloxy-quinazoline

(The reaction is carried out with sodium isopropoxide in isopropanol atambient temperature.)

R_(f) value: 0.70 (silica gel, cyclohexane/ethyl acetate=3:1)

Mass spectrum (ESI⁺): m/z=237, 239 [M+H]⁺

(7) 2-chloromethyl-4-phenyloxy-quinazoline

(The reaction is carried out with sodium hydride and phenol intetrahydrofuran at ambient temperature.)

R_(f) value: 0.65 (silica gel, cyclohexane/ethyl acetate=3:1)

Mass spectrum (ESI⁺): m/z=271, 273 [M+H]⁺

EXAMPLE XLIII1-(2-{2-[(ethoxycarbonyl)methylamino]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

A solution of 110 μL of ethyl diazoacetate in 0.5 ml of toluene is addeddropwise to 531 mg of1-[2-(2-amino-phenyl)-2-oxo-ethyl]-3-methyl-7-((E)-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthineand 10 mg of methyltrioxorhenium in 4.5 ml of toluene at ambienttemperature under an argon atmosphere. The reaction mixture is stirredfor 15 hours at ambient temperature. Then approx. another 5 mg ofmethyl-trioxorhenium and 20 μL ethyl diazoacetate are added and thereaction mixture is heated to 50° C. for two hours. After cooling toambient temperature another 5 mg of methyltrioxorhenium and 20 μL ethyldiazoacetate are added. After another 16 hours at ambient temperaturethe reaction mixture is combined with 5 ml of conc. aqueous ammonia,shaken thoroughly and added to an Extrelut pack. After 15 min it isrinsed with 200 ml methylene chloride. The methylene chloride solutionis evaporated down and chromatographed through a silica gel column withcyclohexane/ethyl acetate/isopropanol (8:2:0 to 8:1:1) as eluant.

Yield: 220 mg (36% of theory)

R_(f) value: 0.40 (silica gel, cyclohexane/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=638 [M+H]⁺

EXAMPLE XLIV1-[(2-cyano-benzofuran-3-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

A mixture of 215 mg of1-{2-[2-cyanomethoxy-phenyl]-2-oxo-ethyl}-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthineand 244 mg of caesium carbonate in 4 ml of N,N-dimethylformamide isstirred for two hours at 50° C., then a further three hours at 70° C.For working up the reaction mixture is combined with water and theprecipitate formed is suction filtered and dried.

Yield: 130 mg (62% of theory)

Mass spectrum (ESI⁺): m/z=572 [M+H]⁺

EXAMPLE XLV1-[2-(3-methyl-2-oxo-2,3-dihydro-1H-benzoimidazol-4-yl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

Prepared by treating1-[2-(1-ethoxycarbonyl-3-methyl-2-oxo-2,3-dihydro-1H-benzoimidazol-4-yl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthinewith 1 N sodium hydroxide solution in methanol at ambient temperature.

R_(f) value: 0.36 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=605 [M+H]⁺

EXAMPLE XLVI 4-acetyl-1-ethoxycarbonyl-1,3-dihydro-benzoimidazol-2-one

5.29 g of diethyldicarbonat and 611 mg of dimethylaminopyridine areadded to 1.50 g of 1-(2,3-diamino-phenyl)-ethanone in 75 ml methylenechloride. The reaction mixture is stirred for three hours at ambienttemperature, then another 100 mg of dimethylaminopyridine and 1 ml ofdiethyldicarbonate are added and the mixture is stirred for a further 20hours at ambient temperature. For working up the reaction mixture isdiluted with methylene chloride, washed with 2 N citric acid solution aswell as saturated sodium hydrogen carbonate solution and saturatedsodium chloride solution, dried over magnesium sulphate and evaporateddown. The residue is chromatographed through a silica gel column withpetroleum ether/ethyl acetate (3:1 to 1:2) as eluant. The desiredproduct is stirred with a little tert.-butylmethylether, suctionfiltered, nachwashed with a little ethyl acetate andtert.-butylmethylether and dried.

Yield: 900 mg (36% of theory)

R_(f) value: 0.15 (silica gel, petroleum ether/ethyl acetate=2:1)

Mass spectrum (ESI⁺): m/z=249 [M+H]⁺

EXAMPLE XLVII1-[(4-amino-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxy-carbonylamino)-piperidin-1-yl]-xanthine

501 mg of1-cyanomethyl-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthineare added to a mixture of 17 mg of potassium-tert. butoxide in 10 ml ofmethanol. After brief heating with stirring a clear solution is formedand after about 20 minutes the nitrile has largely reacted to form theiminoester according to thin layer chromatography. 206 mg of2-amino-benzamidine-hydrochloride are then added and the reactionmixture is refluxed for four hours. After cooling to ambient temperaturethe precipitate formed is suction filtered, washed with methanol anddried.

Yield: 143 mg (23% of theory)

R_(f) value: 0.15 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=574 [M+H]⁺

EXAMPLE XLVIII1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-((Z)-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl-xanthine

150 mg of1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxy-carbonylamino)-piperidin-1-yl]-xanthineare hydrogenated in a mixture of 5 ml of tetrahydrofuran and 5 ml ofmethanol in the presence of 30 mg of 5% m palladium on activatedcharcoal (contaminated with quinoline) at ambient temperature, until thecalculated amount of hydrogen has been taken up. Then a spatula tip ofactivated charcoal is added and the mixture is suction filtered. Thefiltrate is evaporated down and the crude product is purified bychromatography over a silica gel column with cyclohexane/ethyl acetate(7:3 to 4:6).

Yield: 120 mg (85% of theory)

R_(f) value: 0.40 (silica gel, cyclohexane/ethyl acetate=4:6)

Mass spectrum (ESI⁺): m/z=537 [M+H]⁺

EXAMPLE XLIX 8-hydroxymethyl-5-methoxy-quinoline

148 mg of sodium hydride (approx. 60% in mineral oil) are addedbatchwise to a solution of 640 mg of 8-hydroxymethyl-quinolin-5-ol inN,N-dimethylformamide while cooling with an ice bath and the reactionmixture is slowly heated to ambient temperature. After the developmentof gas has ended, 230 μl methyl iodide are added dropwise while coolingwith an ice bath, then the reaction mixture is stirred for approx.another two hours at ambient temperature. For working up it is pouredonto ice water, saturated with sodium chloride and extracted with amixture of diethyl ether and ethyl acetate. The combined extracts arewashed with saturated sodium chloride solution, dried over magnesiumsulphate and evaporated down. The flask residue is triturated withpetroleum ether and the supernatant is decanted. The crude product ispurified through a silica gel column with ethyl acetate as eluant.

Yield: 470 mg (68% of theory)

R_(f) value: 0.70 (silica gel, ethyl acetate)

Mass spectrum (ESI⁺): m/z=190 [M+H]⁺

The following compounds are obtained analogously to Example XLIX:

(1) 8-hydroxymethyl-5-methoxy-isoquinoline

R_(f) value: 0.40 (silica gel, methylene chloride/methanol=10:1)

Mass spectrum (ESI⁺): m/z=190 [M+H]⁺

EXAMPLE L 8-hydroxymethyl-quinolin-5-ol

3.40 g of quinolin-5-ol is combined with 8 ml of conc. hydrochloric acidand 8 ml of 37% formalin solution while cooling with an ice bath. Thenhydrogen chloride gas is piped through the reaction mixture for abouttwo hours, while the temperature slowly rises. The reaction mixture isstirred first overnight while cooling with an ice bath, then at ambienttemperature and then evaporated down in vacuo. The flask residue istaken up in water, covered with a layer of diethyl ether and adjusted topH 10 while cooling with an ice bath and vigorously stirring with diluteammonia solution. After another two hours' vigorous stirring at ambienttemperature the organic phase is separated off and the aqueous phase isextracted with diethyl ether. The combined organic phases are washedwith water and saturated sodium chloride solution, dried over magnesiumsulphate and evaporated down. The flask residue is chromatographedthrough a silica gel column with methylene chloride/methanol (20:1) aseluant.

Yield: 660 mg (16% of theory)

Mass spectrum (ESI⁺): m/z=176 [M+H]⁺

The following compounds are obtained analogously to Example L:

(1) 8-hydroxymethyl-isoquinolin-5-ol

R_(f) value: 0.50 (silica gel, methylene chloride/methanol=5:1)

Mass spectrum (ESI⁺): m/z=176 [M+H]⁺

EXAMPLE LI1-[(2-cyclopropyl-quinazolin-4-yl)methyl]-3-methyl-7-[(1-cyclopenten-1-yl)methyl]-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine

A mixture of 250 mg of1-(2-{2-[(cyclopropylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-[(1-cyclopenten-1-yl)methyl]-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthineand 7.5 ml of ethanolic ammonia solution (6 M) is heated to 150° C. forseven hours in a bomb. For working up the reaction mixture is evaporateddown and chromatographed through a silica gel column with methylenechloride/methanol (100:0 to 70:30) as eluant. The contaminated productfraction is evaporated down and again purified through a reversed phaseHPLC column with water/acetonitrile/trifluoroacetic acid (65:15:0.08 to0:100:0.1) as eluant. The product fractions are evaporated down, madealkaline with dilute sodium hydroxide solution and extracted withmethylene chloride. The combined extracts are dried over magnesiumsulphate and evaporated down.

Yield: 40 mg (14% of theory)

R_(f) value: 0.40 (silica gel, methylene chloride/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=627 [M+H]⁺

EXAMPLE LII4-(2-bromo-acetyl)-1,3-bis-[(2-trimethylsilanyl-ethoxy)methyl]-1,3-dihydro-benzoimidazol-2-one

520 mg of 2-pyrrolidinone-hydrotribromide and 89 mg of 2-pyrrolidinoneare added to 420 mg of4-acetyl-1,3-bis-[(2-trimethylsilanyl-ethoxy)methyl]-1,3-dihydro-benzoimidazol-2-onein 5 ml of tetrahydrofuran under an argon atmosphere. The reactionmixture is refluxed for two hours and then suction filtered while stillwarm. The filter cake is washed with tetrahydrofuran and the filtrate isevaporated down, leaving 660 mg of a yellowish-brown solid. This isstirred with a little methanol, suction filtered, washed with somemethanol and dried. The crude product is reacted further without anymore purification.

Yield: 430 mg (87% of theory)

R_(f) value: 0.23 (silica gel, petroleum ether/ethyl acetate=9:1)

Mass spectrum (EI): m/z=514, 516 [M]⁺

The following compounds are obtained analogously to Example LII:

(1) 7-(2-bromo-acetyl)-1-(tert.-butyloxycarbonyl)-1H-indole

R_(f) value: 0.33 (silica gel, petroleum ether/ethyl acetate=9:1)

Mass spectrum (ESI⁺): m/z=338, 340 [M+H]⁺

(2) 2-bromo-1-(3-isopropyloxy-phenyl)-ethanone

(Carried out with phenyltrimethylammonium tribromide in methylenechloride)

R_(f) value: 0.39 (silica gel, cyclohexane/ethyl acetate=9:1)

(3) 2-bromo-1-(3-difluoromethoxy-phenyl)-ethanone

(Carried out with phenyltrimethylammonium tribromide in methylenechloride)

R_(f) value: 0.24 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:1)

EXAMPLE LIII methyl 3-methyl-imidazo[1,2-a]pyridine-2-carboxylate

A mixture of 1.91 g of 2-aminopyridine and 4.40 g of methyl3-bromo-2-oxo-butyrate in 40 ml of ethanol is refluxed for 6 hours andthen left to stand for 2 days at ambient temperature. The solvent isdistilled off using the rotary evaporator and the crude product ispurified by chromatography over a silica gel column with methylenechloride/methanol/methanolic ammonia solution (95:4:1 to 90:9:1) aseluant. 560 mg of the ethyl ester are isolated as the by-product.

Yield: 2.09 g (54% of theory)

R_(f) value: 0.20 (silica gel, methylene chloride/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=191 [M+H]⁺

EXAMPLE LIV 2-chloromethyl-4-isopropyl-quinazoline

Dry hydrogen chloride gas is piped through a solution of 2.86 g of1-(2-amino-phenyl)-2-methyl-propan-1-one and 1.33 ml ofchloroacetonitrile in 14 ml dioxane with stirring at ambient temperaturefor approx. five hours. Then the dioxane is largely distilled off in awater jet vacuum. The honey-like residue is combined with ice water andthe resulting suspension is made alkaline with saturated potassiumcarbonate solution while cooling with an ice bath. The precipitate issuction filtered, washed with water and dried. The crude product ispurified by chromatography over a silica gel column with petroleumether/methylene chloride (8:2 to 0:1) as eluant.

Yield: 1.80 g (58% of theory)

R_(f) value: 0.30 (silica gel, methylene chloride/petroleum ether=1:1)

Mass spectrum (ESI⁺): m/z=221, 223 [M+H]⁺

EXAMPLE LV 1-chloromethyl-3-trifluoromethyl-3,4-dihydro-isoquinoline

530 mg of N-(1-benzyl-2,2,2-trifluoro-ethyl)-2-chloro-acetamide(prepared by reacting 1-benzyl-2,2,2-trifluoro-ethylamine withchloroacetyl chloride in the presence of triethylamine) and 0.74 ml ofphosphorus oxychloride are added to 4.00 g of polyphosphoric acid. Theviscous mixture is stirred for 1.5 hours at 130° C. For working up thereaction mixture is cooled and combined with ice water, stirredvigorously for ten minutes and suction filtered. The filter cake isdissolved in ethyl acetate and the solution is dried over magnesiumsulphate and evaporated down, leaving a white solid.

Yield: 415 mg (84% of theory)

R_(f) value: 0.55 (aluminium oxide, petroleum ether/ethyl acetate=10:1)

Mass spectrum (ESI⁺): m/z=248, 250 [M+H]⁺

The following compound is obtained analogously to Example LV:

(1) 1-methyl-3-trifluoromethyl-3,4-dihydro-isoquinoline

(The starting material N-(1-benzyl-2,2,2-trifluoro-ethyl)-acetamide isobtained by reacting 1-benzyl-2,2,2-trifluoro-ethylamine with aceticanhydride.)

EXAMPLE LVI 3-bromomethyl-1-(1-cyano-1-methyl-ethyl)-isoquinoline

A mixture of 375 mg of 1-(1-cyano-1-methyl-ethyl)-3-methyl-isoquinolineand 321 mg of N-bromosuccinimide in 5 ml carbon tetrachloride iscombined with a spatula tip of 2,2-azoisobutyric acid dinitrile andrefluxed for about six hours. The cooled reaction mixture is filteredand evaporated down. The flask residue is reacted further without anymore purification.

R_(f) value: 0.70 (silica gel, cyclohexane/ethyl acetate=3:1)

The following compounds are obtained analogously to Example LVI:

(1)6-bromomethyl-1-[(2-trimethylsilanyl-ethoxy)methyl]-1H-quinolin-2-one(2) 1-bromomethyl-4-bromo-3-methoxy-isoquinoline (3)2-bromomethyl-[1,5]naphthyridine

Mass spectrum (ESI⁺): m/z=223, 225 [M+H]⁺

(4) 5-bromomethyl-[1,6]naphthyridine

R_(f) value: 0.48 (silica gel, ethyl acetate/methanol=98:2)

(5) 7-bromomethyl-5-phenyl-quinoxaline

R_(f) value: 0.85 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=299, 301 [M+H]⁺

(6) 4-bromomethyl-[1,5]naphthyridine

R_(f) value: 0.56 (silica gel, methylene chloride/ethyl acetate=7:3)

Mass spectrum (ESI⁺): m/z=223, 225 [M+H]⁺

(7) 1-bromomethyl-3-trifluoromethyl-isoquinoline

Mass spectrum (ESI⁺): m/z=290, 292 [M+H]⁺

(8) 1-bromomethyl-3-difluoromethyl-isoquinoline

Mass spectrum (ESI⁺): m/z=272, 274 [M+H]⁺

(9) 1-bromomethyl-4-chloro-3-methoxy-isoquinoline EXAMPLE LVII1-(1-cyano-1-methyl-ethyl)-3-methyl-isoquinoline

3.30 g of 2,2-azoisobutyric acid dinitrile are added to 1.60 g of3-methyl-isoquinoline-N-oxide in 30 ml of toluene. The reaction mixtureis stirred for six hours at 85° C. and then left to stand for two daysat ambient temperature. For working up the reaction mixture is extractedwith 20% hydrochloric acid. The combined aqueous phases are diluted withmethylene chloride, made alkaline with saturated potassium carbonatesolution while cooling with an ice bath and extracted with methylenechloride. The combined methylene chloride extracts are dried overmagnesium sulphate and evaporated down. The residue is chromatographedthrough a silica gel column with cyclohexane as eluant.

Yield: 375 mg (18% of theory)

Mass spectrum (ESI⁺): m/z=211 [M+H]⁺

R_(f) value: 0.75 (silica gel, cyclohexane/ethyl acetate=3:1)

EXAMPLE LVIII1-(2-cyanoimino-2-phenyl-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthine(E/Z-mixture)

0.48 ml of a 1M solution of titanium tetrachloride in methylene chlorideare added dropwise to 244 mg of1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxy-carbonylamino)-piperidin-1-yl]-xanthinein 7 ml of methylene chloride. Then 88 μl of1,3-bis(trimethylsilyl)carbodiimide are added and the mixture is stirredfor four hours at ambient temperature. For working up the reactionmixture is diluted with methylene chloride and poured onto ice water.The organic phase is washed with 0.5 N citric acid, dried over magnesiumsulphate and evaporated down. The crude product is purified bychromatography over a silica gel column with methylene chloride/methanol(98:2 to 95:5) as eluant.

Yield: 206 mg (97% of theory)

Mass spectrum (ESI⁻): m/z=557 [M−H]⁻

R_(f) value: 0.16 (silica gel, cyclohexane/ethyl acetate=1:1)

EXAMPLE LIX1-[(1H-benzoimidazol-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxy-carbonylamino)-piperidin-1-yl]-xanthine

350 mg of1-[(2-amino-phenylaminocarbonyl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthineare refluxed in 3 ml glacial acetic acid for two hours. Then thereaction mixture is evaporated down, the flask residue is combined with5 ml of 1 M sodium hydroxide solution and washed with methylenechloride. Then the aqueous phase is acidified with 1 M hydrochloric acidand extracted with methylene chloride. The combined extracts areevaporated down and chromatographed through a silica gel column withcyclohexane/ethyl acetate/methanol (6:4:0 to 5:4:1) as eluant.

Yield: 250 mg of (74% of theory)

Mass spectrum (ESI⁺): m/z=547 [M+H]⁺

EXAMPLE LX Ethyl 3,4-dimethyl-6,7-dihydro-5H-[2]pyrindin-1-carboxylate

Prepared by treating 1.16 g of ethyl3,4-dimethyl-4a-(pyrrolidin-1-yl)-5,6,7,7a-tetrahydro-4aH-[2]pyrindin-1-carboxylatewith 1.08 g of 70% 3-chloro-perbenzoic acid in 50 ml methylene chlorideat ambient temperature.

Yield: 850 mg (97% of theory)

R_(f) value: 0.30 (aluminium oxide, petroleum ether/ethyl acetate=5:1)

Mass spectrum (ESI⁺): m/z=220 [M+H]⁺

The following compounds are obtained analogously to Example LX:

(1) ethyl 3,4-dimethyl-5,6,7,8-tetrahydro-isoquinoline-1-carboxylate

R_(f) value: 0.35 (aluminium oxide, petroleum ether/ethyl acetate=5:1)

Mass spectrum (ESI⁺): m/z=234 [M+H]⁺

EXAMPLE LXI Ethyl3,4-dimethyl-4a-(pyrrolidin-1-yl)-5,6,7,7a-tetrahydro-4aH-[2]pyrindin-1-carboxylate

Prepared by reacting 2.50 g of ethyl5,6-dimethyl-[1,2,4]triazin-3-carboxylate with 2.74 g of1-(cyclopenten-1-yl)-pyrrolidine in 25 ml chloroform at ambienttemperature.

Yield: 3.00 g (75% of theory)

R_(f) value: 0.60 (aluminium oxide, petroleum ether/ethyl acetate=5:1)

Mass spectrum (ESI⁺): m/z=291 [M+H]⁺

The following compounds are obtained analogously to Example LXI:

(1) ethyl3,4-dimethyl-4a-(pyrrolidin-1-yl)-4a,5,6,7,8,8a-hexahydro-isoquinoline-1-carboxylate

R_(f) value: 0.60 (aluminium oxide, petroleum ether/ethyl acetate=5:1)

Mass spectrum (ESI⁺): m/z=305 [M+H]⁺

EXAMPLE LXII Methyl 2,3,8-trimethyl-quinoxalin-6-carboxylate

Prepared by reacting 1.60 g of methyl 3,4-diamino-5-methyl-benzoate with0.86 ml diacetyl in a mixture of water and ethanol while refluxing.

Yield: 1.53 g (80% of theory)

R_(f) value: 0.63 (silica gel, cyclohexane/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=231 [M+H]⁺

The following compounds are obtained analogously to Example LXII:

(1) methyl 8-methyl-quinoxalin-6-carboxylate

(reaction is carried out with glyoxal in water.)

R_(f) value: 0.55 (silica gel, cyclohexane/ethyl acetate=1:1)

Mass spectrum (ESI⁺): m/z=203 [M+H]⁺

(2) 5-bromo-7-methyl-quinoxaline

(reaction is carried out with glyoxal in a water/ethanol mixture.)

R_(f) value: 0.75 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=223, 225 [M+H]⁺

EXAMPLE LXIII Methyl 3,4-diamino-5-methyl-benzoate

Prepared by reduction of methyl 3-nitro-4-amino-5-methyl-benzoate at apartial hydrogen pressure of 50 psi in the presence of Raney nickel inmethanol at ambient temperature.

R_(f) value: 0.40 (silica gel, tert.-butylmethylether)

EXAMPLE LXIV Methyl 3-nitro-4-amino-5-methyl-benzoate

Prepared by treating 3-nitro-4-acetylamino-5-methyl-benzoic acid withhydrogen chloride gas in methanol at ambient temperature andsubsequently heating while refluxing.

Mass spectrum (ESI⁺): m/z=211 [M+H]⁺

R_(f) value: 0.75 (silica gel, tert.-butylmethylether/acetic acid=99:1)

EXAMPLE LXV1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-((E)-1-buten-1-yl)-8-bromo-xanthine

0.13 ml 35% hydrogen peroxide solution are added to 290 mg of1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-(1-phenylsulphanyl-butyl)-8-bromo-xanthinein 6 ml hexafluoroisopropanol. The reaction mixture is stirred for onehour at ambient temperature, diluted with methylene chloride and washedwith sodium thiosulphate solution. The organic phase is dried overmagnesium sulphate and evaporated down. The flask residue is taken up in6 ml of toluene and refluxed for eight hours. Then the toluene isdistilled off in vacuo and the crude product is purified through asilica gel column with methylene chloride/methanol (100:0 to 95:5) aseluant.

Yield: 104 mg (45% of theory)

R_(f) value: 0.61 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=417, 419 [M+H]⁺

The following compounds are obtained analogously to Example LXV:

(1) 3-methyl-7-(3-methyl-1-buten-1-yl)-8-bromo-xanthine

R_(f) value: 0.24 (silica gel, methylene chloride/methanol=95:5)

Mass spectrum (ESI⁺): m/z=313, 315 [M+H]⁺

EXAMPLE LXVI 1-methanesulphonyloxymethyl-4-difluoromethoxy-naphthalene

Prepared by reacting (4-difluoromethoxy-naphthalen-1-yl)-methanol withmethanesulphonic acid chloride in methylene chloride in the presence oftriethylamine.

The following compounds are obtained analogously to Example LXVI:

-   (1) (E)-1-methanesulphonyloxy-3-(2-nitro-phenyl)-2-propene-   (2) (E)-1-methanesulphonyloxy-3-pentafluorophenyl-2-propene-   (3) (E)-1-methanesulphonyloxy-3-(2-trifluoromethyl-phenyl)-2-propene-   (4) (E)-1-methanesulphonyloxy-3-(3-trifluoromethyl-phenyl)-2-propene-   (5) (E)-1-methanesulphonyloxy-3-(4-trifluoromethyl-phenyl)-2-propene

EXAMPLE LXVII 7-methyl-5-phenyl-quinoxaline

A mixture of 400 mg of 5-bromo-7-methyl-quinoxaline, 244 mg ofphenylboric acid and 100 mg of tetrakis(triphenylphosphine)palladium in12 ml dioxane, 4 ml of methanol and 3.6 ml 1 M aqueous sodium carbonatesolution is refluxed for three hours under an argon atmosphere. Then thereaction mixture is evaporated down and the residue is distributedbetween ethyl acetate and water. The ethyl acetate phase is separatedoff, dried over magnesium sulphate and evaporated down. The crudeproduct is purified by chromatography over a silica gel column withcyclohexane/ethyl acetate (85:15 to 70:30) as eluant.

Yield: 390 mg (66% of theory)

R_(f) value: 0.36 (silica gel, petroleum ether/ethyl acetate=5:1)

Mass spectrum (ESI⁺): m/z=221 [M+H]⁺

EXAMPLE LXVIII 1-methyl-3-trifluoromethyl-isoquinoline

Prepared by treating 905 mg of1-chloromethyl-3-trifluoromethyl-3,4-dihydro-isoquinoline with 420 mg ofpotassium-tert. butoxide in 10 ml of tetrahydrofuran at ambienttemperature.

Yield: 755 mg of (98% of theory)

Mass spectrum (ESI⁺): m/z=212 [M+H]⁺

The following compounds are obtained analogously to Example LXVIII:

(1) 1-methyl-3-difluoromethyl-isoquinoline

(Prepared from 1-methyl-3-trifluoromethyl-3,4-dihydro-isoquinoline)

Mass spectrum (ESI⁺): m/z=194 [M+H]⁺

EXAMPLE LXIX 4-chloro-3-methoxy-1-methyl-isoquinoline

Prepared by treating 3-methoxy-1-methyl-isoquinoline with sulphurylchloride in methylene chloride.

R_(f) value: 0.30 (silica gel, cyclohexane)

Mass spectrum (ESI⁺): m/z=208, 210 [M+H]⁺

EXAMPLE LXX 3-cyclopropyl-8-bromo-xanthine

Prepared by reacting 3-cyclopropyl-xanthine with bromine in the presenceof potassium carbonate in acetonitrile at 60° C.

R_(f) value: 0.65 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:1)

Mass spectrum (ESI⁺): m/z=271, 273 [M+H]⁺

EXAMPLE LXXI Ethyl 1,2,3,4-tetrahydro-phenanthridin-6-yl-carboxylate

Analogously to the method described by Gonsalves et al. (Tetrahedron1992, 48, 6821) a solution of 3.90 g of ethyl5,6,7,8-tetrahydro-benzo[1,2,4]triazin-3-carboxylate (Sagi et al.,Heterocycles 1989, 29, 2253) in 20 ml dioxane is refluxed. Then 8.22 gof anthranilic acid and 7.02 g of isoamylnitrite, in each case dissolvedin 20 ml dioxane, are simultaneously added dropwise within 25 minutes bymeans of two dropping funnels. The reaction mixture is refluxed for afurther 30 minutes. For working up the cooled deep-brown reactionsolution is diluted with 150 ml diethyl ether, washed with 100 ml of 2 Nsodium hydroxide solution and with water, dried over magnesium sulphateand evaporated down. The brown, oily flask residue is chromatographedthrough a silica gel column with ethyl acetate/petroleum ether (20:80 to50:50) as eluant. The product obtained is still somewhat contaminated,but is reacted further without any more purification.

Yield: 380 mg (8% of theory)

R_(f) value: 0.55 (silica gel, petroleum ether/ethyl acetate=2:1)

Mass spectrum (ESI⁺): m/z=256 [M+H]⁺

Preparation of the final compounds:

EXAMPLE 11,3-dimethyl-7-(2,6-dicyano-benzyl)-8-(3-amino-piperidin-1-yl)-xanthine

129 mg of 3-amino-piperidine-dihydrochloride are added to a mixture of298 mg of 1,3-dimethyl-7-(2,6-dicyano-benzyl)-8-bromo-xanthine and 420mg of potassium carbonate in 9 ml of N,N-dimethylformamide. The reactionmixture is stirred for three hours at 80° C. For working up the mixtureis diluted with methylene chloride and washed with saturated sodiumchloride solution. The organic phase is dried over magnesium sulphateand evaporated down. The crude product is purified by chromatographythrough a silica gel column with methylene chloride/methanol/conc.methanolic ammonia (95:5:1 to 80:20:1) as eluant.

Yield: 43 mg (14% of theory)

R_(f) value: 0.67 (silica gel, methylene chloride/methanol/conc. aqueousammonia=80:20:1)

Mass spectrum (ESI⁺): m/z=419 [M+H]⁺

The following compounds are obtained analogously to Example 1:

(1)1-(2-cyano-ethyl)-3-methyl-7-(2-cyano-benzyl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.35 (silica gel, methylene chloride/methanol=9:1)

Mass spectrum (ESI⁺): m/z=433 [M+H]⁺

EXAMPLE 21-(2-{2-[(ethoxycarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

A solution of 209 mg of1-(2-{2-[(ethoxycarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthinein 4 ml methylene chloride is combined with 1 ml of trifluoroacetic acidand stirred for half an hour at ambient temperature. For working up thereaction mixture is diluted with methylene chloride and washed withsaturated potassium carbonate solution. The organic phase is dried,evaporated down and chromatographed through a silica gel column withmethylene chloride/methanol (1:0 to 4:1) as eluant.

Yield: 153 mg of (87% of theory)

Mass spectrum (ESI⁺): m/z=553 [M+H]⁺

The following compounds are obtained analogously to Example 2:

(1)1-(2-{2-[(aminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=524 [M+H]⁺

(2)1-(2-{3-[(methanesulphinyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.58 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=100:100:0.1)

Mass spectrum (ESI⁺): m/z=543 [M+H]⁺

(3)1-(1-methyl-2-oxo-2-phenyl-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=465 [M+H]⁺

(4)1-(2-phenoxy-ethyl)-3-methyl-7-(2-cyano-benzyl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.50 (silica gel, methylene chloride/methanol=9:1)

Mass spectrum (ESI⁺): m/z=500 [M+H]⁺

(5)1-(2-phenyl-2-oxo-ethyl)-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.58 (silica gel, methylene chloride/methanol/conc. aqueousammonia=80:20:1)

Mass spectrum (ESI⁻): m/z=435 [M−H]⁻

(6)1-(2-{3-[(ethoxycarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=553 [M+H]⁺

(7)1-(2-{2-[(methylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=538 [M+H]⁺

(8)1-(2-{2-[(dimethylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=552 [M+H]⁺

(9)1-(2-methoxy-ethyl)-3-methyl-7-(2-cyano-benzyl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.40 (silica gel, methylene chloride/methanol=9:1)

Mass spectrum (ESI⁺): m/z=438 [M+H]⁺

(10)1-methyl-3-[(methoxycarbonyl)methyl]-7-(2-cyano-benzyl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.40 (silica gel, methylene chloride/methanol=9:1)

Mass spectrum (ESI⁺): m/z=452 [M+H]⁺

(11)1-methyl-3-cyanomethyl-7-(2-cyano-benzyl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.20 (silica gel, methylene chloride/methanol=9:1)

Mass spectrum (ESI⁺): m/z=419 [M+H]⁺

(12)1-methyl-3-(2-propyn-1-yl)-7-(2-cyano-benzyl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.40 (silica gel, methylene chloride/methanol=9:1)

Mass spectrum (ESI⁺): m/z=418 [M+H]⁺

(13)1-{2-[3-(2-oxo-imidazolidin-1-yl)-phenyl]-2-oxo-ethyl}-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.54 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=100:100:0.1)

Mass spectrum (ESI⁺): m/z=535 [M+H]⁺

(14)1-methyl-3-(2-propen-1-yl)-7-(2-cyano-benzyl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.40 (silica gel, methylene chloride/methanol=9:1)

Mass spectrum (ESI⁺): m/z=420 [M+H]⁺

(15)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=435 [M+H]⁺

(16)1-(2-{2-[(ethylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.50 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=100:100:0.1)

Mass spectrum (ESI⁺): m/z=522 [M+H]⁺

(17)1-methyl-3-phenyl-7-(2-cyano-benzyl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.40 (silica gel, methylene chloride/methanol=9:1)

Mass spectrum (ESI⁺): m/z=456 [M+H]⁺

(18)1-[2-(2-amino-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.50 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:0.1)

Mass spectrum (ESI⁺): m/z=466 [M+H]⁺

(19)1-(2-phenyl-2-oxo-ethyl)-3-cyanomethyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.07 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=476 [M+H]⁺

(20)1-[(quinolin-2-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.50 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=474 [M+H]⁺

(21)1-[(2-oxo-2H-chromen-4-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

Mass spectrum (ESI⁺): m/z=491 [M+H]⁺

R_(f) value: 0.16 (silica gel, methylene chloride/methanol/conc. aqueousammonia=95:5:0.1)

(22)1-[(cinnolin-4-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine(1:1 mixture with1-[(1,4-dihydro-cinnolin-4-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine)

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.49 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=475 [M+H]⁺

(23)1-[(1-methyl-2-oxo-1,2-dihydro-quinolin-4-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

Melting point: 178-181° C.

Mass spectrum (ESI⁺): m/z=504 [M+H]⁺

(24)1-[(4-oxo-3,4-dihydro-phthalazin-1-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.06 (silica gel, methylene chloride/methanol/conc. aqueousammonia=95:5:0.1)

Mass spectrum (ESI⁺): m/z=491 [M+H]⁺

(25)1-[(quinazolin-4-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.48 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=475 [M+H]⁺

(26)1-[(5-methyl-3-phenyl-isoxazol-4-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.40 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:0.1)

Mass spectrum (ESI⁺): m/z=504 [M+H]⁺

(27)1-[(isoquinoline-3-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.51 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=474 [M+H]⁺

(28)1-[(3-phenyl-[1,2,4]oxadiazol-5-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.23 (silica gel, methylene chloride/methanol/conc. aqueousammonia=95:5:1)

Mass spectrum (ESI⁺): m/z=491 [M+H]⁺

(29)1-[(4-phenyl-pyridin-2-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.51 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=500 [M+H]⁺

(30)1-[(5-phenyl-pyridin-2-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.58 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=500 [M+H]⁺

(31)1-[(3-methyl-4-oxo-3,4-dihydro-phthalazin-1-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine-hydrochloride

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride; product precipitated as the hydrochloride)

R_(f) value: 0.55 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:0.1)

Mass spectrum (ESI⁺): m/z=505 [M+H]⁺

(32)1-[2-(3-methylsulphanyl-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.34 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=497 [M+H]⁺

(33)1-[2-(3-methanesulphinyl-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.21 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=513 [M+H]⁺

(34)1-[2-(3-methanesulphonyl-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.66 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:1)

Mass spectrum (ESI⁺): m/z=529 [M+H]⁺

(35)1-[2-(3-carboxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine-hydrochloride

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride; product precipitated as the hydrochloride)

R_(f) value: 0.54 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:1)

Mass spectrum (ESI⁺): m/z=495 [M+H]⁺

(36)1-[2-(3-methoxycarbonyl-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine-hydrochloride

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride; product precipitated as the hydrochloride)

R_(f) value: 0.47 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:1)

Mass spectrum (ESI⁺): m/z=509 [M+H]⁺

(37)1-{2-[3-(methylaminocarbonyl)-phenyl]-2-oxo-ethyl}-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine-hydrochloride

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride; product obtained as the hydrochloride)

R_(f) value: 0.53 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:1)

Mass spectrum (ESI⁺): m/z=508 [M+H]⁺

(38)1-{2-[3-(dimethylaminocarbonyl)-phenyl]-2-oxo-ethyl}-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine-hydrochloride

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride; product obtained as the hydrochloride)

R_(f) value: 0.53 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:1)

Mass spectrum (ESI⁺): m/z=522 [M+H]⁺

(39)1-{2-[3-(morpholin-4-yl-carbonyl)-phenyl]-2-oxo-ethyl}-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine-hydrochloride

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride; product obtained as the hydrochloride)

R_(f) value: 0.53 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:1)

Mass spectrum (ESI⁺): m/z=564 [M+H]⁺

(40)1-[2-(2-carboxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine-hydrochloride

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride; product obtained as the hydrochloride)

R_(f) value: 0.53 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:1)

Mass spectrum (ESI⁺): m/z=495 [M+H]⁺

(41)1-[2-(2-ethoxycarbonyl-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine-hydrochloride

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride; product obtained as the hydrochloride)

R_(f) value: 0.41 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:1)

Mass spectrum (ESI⁺): m/z=523 [M+H]⁺

(42)1-{2-[2-(dimethylaminocarbonyl)-phenyl]-2-oxo-ethyl}-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine-hydrochloride

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride; product obtained as the hydrochloride)

R_(f) value: 0.53 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:1)

Mass spectrum (ESI⁺): m/z=522 [M+H]⁺

(43)1-{2-[2-(morpholin-4-yl-carbonyl)-phenyl]-2-oxo-ethyl}-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine-hydrochloride

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride; product obtained as the hydrochloride)

R_(f) value: 0.53 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:1)

Mass spectrum (ESI⁺): m/z=564 [M+H]⁺

(44)1-[2-(2,6-dimethoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine-hydrochloride

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride; product obtained as the hydrochloride)

R_(f) value: 0.44 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:1)

Mass spectrum (ESI⁺): m/z=511 [M+H]⁺

(45)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-(2,3-dimethyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine-hydrochloride

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride; product obtained as the hydrochloride)

R_(f) value: 0.68 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:1)

Mass spectrum (ESI⁺): m/z=465 [M+H]⁺

(46)1-((E)-3-phenyl-allyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.38 (silica gel, methylene chloride/methanol/conc. aqueousammonia=95:5:0.1)

Mass spectrum (ESI⁺): m/z=449 [M+H]⁺

(47)1-[(benzo[b]thiophen-3-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.51 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=479 [M+H]⁺

(48)1-[(1H-indol-3-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.48 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=462 [M+H]⁺

(49)1-[(biphenyl-4-yl)methyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.30 (silica gel, methylene chloride/methanol/conc. aqueousammonia=95:5:0.1)

Mass spectrum (ESI⁺): m/z=499 [M+H]⁺

(50)1-[(1-naphthyl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.56 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=457 [M+H]⁺

(51)1-[(1-methyl-2-oxo-1,2-dihydro-quinolin-4-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.40 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=488 [M+H]⁺

(52)1-[(quinolin-4-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.52 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=458 [M+H]⁺

(53)1-(2-cyclohexyl-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.48 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=457 [M+H]⁺

(54)1-(3,3-dimethyl-2-oxo-butyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.49 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=431 [M+H]⁺

(55)1-[(quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.20 (silica gel, methylene chloride/methanol/conc. aqueousammonia=95:5:0.1)

Mass spectrum (ESI⁺): m/z=459 [M+H]⁺

(56)1-[(2-methyl-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.25 (silica gel, methylene chloride/methanol/conc. aqueousammonia=95:5:0.1)

Mass spectrum (ESI⁺): m/z=471 [M+H]⁺

(57)1-({5-[(methoxycarbonyl)methylamino]-isoquinolin-1-yl}methyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.43 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=561 [M+H]⁺

(58)1-(2-dimethylamino-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.38 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=418 [M+H]⁺

(59)1-[2-(piperidin-1-yl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.35 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=458 [M+H]⁺

(60)1-[(2-methyl-1-oxo-1,2-dihydro-isoquinoline-4-yl)methyl]-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.17 (silica gel, methylene chloride/methanol/conc. aqueousammonia=95:5:0.1)

Mass spectrum (ESI⁺): m/z=488 [M+H]⁺

(61)1-[(2-methyl-1-oxo-1,2-dihydro-isoquinoline-4-yl)methyl]-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.13 (silica gel, methylene chloride/methanol/conc. aqueousammonia=95:5:0.1)

Mass spectrum (ESI⁺): m/z=504 [M+H]⁺

(62)1-[(2-methoxy-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.17 (silica gel, methylene chloride/methanol/conc. aqueousammonia=95:5:0.1)

Mass spectrum (ESI⁺): m/z=487 [M+H]⁺

(63)1-[(isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.42 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=458 [M+H]⁺

(64)1-[(4-methoxy-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.14 (silica gel, methylene chloride/methanol/conc. aqueousammonia=95:5:0.1)

Mass spectrum (ESI⁺): m/z=487 [M+H]⁺

(65)1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

Melting point: 155-158° C.

Mass spectrum (ESI⁺): m/z=472 [M+H]⁺

(66)1-[2-(2,3-dimethoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.40 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=511 [M+H]⁺

(67)1-[(5-nitro-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.15 (silica gel, methylene chloride/methanol/conc. aqueousammonia=95:5:0.1)

Mass spectrum (ESI⁺): m/z=502 [M+H]⁺

(68)1-[2-(pyrrolidin-1-yl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.56 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=444 [M+H]⁺

(69)1-[(4-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.46 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=472 [M+H]⁺

(70)1-[(2-naphthyl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.20 (silica gel, methylene chloride/methanol/conc. aqueousammonia=95:5:0.1)

Mass spectrum (ESI⁺): m/z=457 [M+H]⁺

(71)1-[(4-oxo-3,4-dihydro-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.38 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:0.1)

Mass spectrum (ESI⁺): m/z=475 [M+H]⁺

(72)1-[(quinolin-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.15 (silica gel, methylene chloride/methanol/conc. aqueousammonia=95:5:0.1)

Mass spectrum (ESI⁺): m/z=458 [M+H]⁺

(73)1-[(4-dimethylamino-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.18 (silica gel, methylene chloride/methanol/conc. aqueousammonia=95:5:0.1)

Mass spectrum (ESI⁺): m/z=500 [M+H]⁺

(74)1-[(isoquinolin-1-yl)methyl]-3-methyl-7-((E)-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride; the product still contains approx. 20% of Z isomer)

R_(f) value: 0.66 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:0.1)

Mass spectrum (ESI⁺): m/z=460 [M+H]⁺

(75)1-[(3-methoxy-naphthalen-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.25 (silica gel, methylene chloride/methanol/conc. aqueousammonia=95:5:0.1)

Mass spectrum (ESI⁺): m/z=487 [M+H]⁺

(76)1-[2-(2,3-dihydro-benzo[1,4]dioxin-5-yl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

Mass spectrum (ESI⁺): m/z=509 [M+H]⁺

(77)1-[(3-methyl-4-oxo-3,4-dihydro-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.20 (silica gel, methylene chloride/methanol/conc. aqueousammonia=95:5:0.1)

Mass spectrum (ESI⁺): m/z=489 [M+H]⁺

(78)1-[2-(3-methyl-2-oxo-2,3-dihydro-benzooxazol-7-yl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.47 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=522 [M+H]⁺

(79)1-[2-(benzo[1,3]dioxol-4-yl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

Mass spectrum (ESI⁺): m/z=495 [M+H]⁺

(80)1-[(quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

Mass spectrum (ESI⁺): m/z=459 [M+H]⁺

(81)1-[(quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

Mass spectrum (ESI⁺): m/z=459 [M+H]⁺

(82)1-[(quinazolin-2-yl)methyl]-3-methyl-7-((E)-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride; the product still contains approx. 20% of Z isomer)

R_(f) value: 0.12 (silica gel, methylene chloride/methanol/conc. aqueousammonia=95:5:0.1)

Mass spectrum (ESI⁺): m/z=461 [M+H]⁺

(83)1-[(quinazolin-2-yl)methyl]-3-methyl-7-((E)-2-buten-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride; the product still contains approx. 15% of Z isomer)

R_(f) value: 0.12 (silica gel, methylene chloride/methanol/conc. aqueousammonia=95:5:0.1)

Mass spectrum (ESI⁺): m/z=461 [M+H]⁺

(84)1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-((E)-2-buten-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride; the product still contains approx. 17% of Z isomer)

R_(f) value: 0.54 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=474 [M+H]⁺

(85)1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-((E)-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride; the product still contains approx. 17% of Z isomer)

R_(f) value: 0.54 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=474 [M+H]⁺

(86)1-(2-{2-[(ethylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=536 [M+H]⁺

(87)1-[2-(2-amino-phenyl)-2-oxo-ethyl]-3-methyl-7-[(1-cyclopenten-1-yl)methyl]-8-(3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=478 [M+H]⁺

(88)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-[(1-cyclopenten-1-yl)methyl]-8-(3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=463 [M+H]⁺

(89)1-(2-{2-[(methylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-[(1-cyclopenten-1-yl)methyl]-8-(3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=550 [M+H]⁺

(90)1-methyl-3-isopropyl-7-(2-cyano-benzyl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.40 (silica gel, methylene chloride/methanol=9:1)

Mass spectrum (ESI⁺): m/z=422 [M+H]⁺

(91)1-(2-{2-[(methylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=522 [M+H]⁺

(92)1-(2-{2-[(aminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=508 [M+H]⁺

(93)1-[2-(2-cyanomethylamino-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.50 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:1)

Mass spectrum (ESI⁺): m/z=505 [M+H]⁺

(94)1-(2-{2-[(isopropylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.30 (silica gel, methylene chloride/methanol=9:1)

Mass spectrum (ESI⁺): m/z=550 [M+H]⁺

(95)1-[(isoquinolin-1-yl)methyl]-3-[(methoxycarbonyl)methyl]-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.21 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=532 [M+H]⁺

(96)1-[2-(2-acetylamino-phenyl)-2-oxo-ethyl]-3-methyl-7-((E)-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(product contains approx. 10% of Z isomer)

Mass spectrum (ESI⁺): m/z=494 [M+H]⁺

(97)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(product contains approx. 25% of Z isomer)

R_(f) value: 0.30 (silica gel, methylene chloride/methanol=9:1)

Mass spectrum (ESI⁺): m/z=437 [M+H]⁺

(98)1-(2-{2-[(isopropyloxycarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=567 [M+H]⁺

(99)1-(2-{2-[(methylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=522 [M+H]⁺

(100)1-(2-{2-[(isopropylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(product contains approx. 10% of Z isomer)

Mass spectrum (ESI⁺): m/z=522 [M+H]⁺

(101)1-(2-{2-[(methylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(product contains approx. 8% of Z isomer)

R_(f) value: 0.51 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:0.1)

Mass spectrum (ESI⁺): m/z=524 [M+H]⁺

(102)1-(2-{2-[(ethylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=536 [M+H]⁺

(103)1-[2-(2-{[(ethoxycarbonylamino)carbonyl]amino}-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=581 [M+H]⁺

(104)1-[2-(2-amino-phenyl)-2-oxo-ethyl]-3-methyl-7-((E)-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.54 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:0.1)

Mass spectrum (ESI⁺): m/z=452 [M+H]⁺

(105)1-[2-(2-acetylamino-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.48 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:0.1)

Mass spectrum (ESI⁺): m/z=508 [M+H]⁺

(106)1-[2-(2-amino-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.31 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=450 [M+H]⁺

(107)1-(2-{2-[(methylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=522 [M+H]⁺

(108)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

(product contains approx. 22% of Z isomer)

Mass spectrum (ESI⁺): m/z=437 [M+H]⁺

(109)1-(2-{2-[(ethylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.40 (silica gel, methylene chloride/methanol=9:1)

Mass spectrum (ESI⁺): m/z=536 [M+H]⁺

(110)1-[2-(2-acetylamino-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.23 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=492 [M+H]⁺

(111)1-(2-{2-[2-oxo-2-(pyrrolidin-1-yl)-ethoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.20 (silica gel, methylene chloride/methanol=9:1)

Mass spectrum (ESI⁺): m/z=562 [M+H]⁺

(112)1-(2-{2-[(methylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=538 [M+H]⁺

(113)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=435 [M+H]⁺

(114)1-(2-{2-[(ethylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

(product contains approx. 30% of Z isomer)

Mass spectrum (ESI⁺): m/z=538 [M+H]⁺

(115) 1-methyl-7-(2-cyano-benzyl)-8-(3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=380 [M+H]⁺

(116)1-(2-{2-[(isopropylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.40 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:0.1)

Mass spectrum (ESI⁺): m/z=536 [M+H]⁺

(117)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine

(product contains approx. 23% of Z isomer)

R_(f) value: 0.42 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:0.1)

Mass spectrum (ESI⁺): m/z=437 [M+H]⁺

(118)1-(2-{2-[(isopropylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.20 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=520 [M+H]⁺

(119)1-[2-(2-acetylamino-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.15 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=492 [M+H]⁺

(120)1-(2-{2-[(isopropylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=520 [M+H]⁺

(121)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-(2-methyl-allyl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.21 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=437 [M+H]⁺

(122)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-(3-bromo-allyl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.14 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=501, 503 [M+H]⁺

(123)1-(2-{2-[(methoxycarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.42 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:0.1)

Mass spectrum (ESI⁺): m/z=524 [M+H]⁺

(124)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-[(furan-2-yl)methyl]-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.23 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=463 [M+H]⁺

(125)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-(2-chloro-allyl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.18 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

(126)1-{2-[2-(1-methoxycarbonyl-ethoxy)-phenyl]-2-oxo-ethyl}-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=537 [M+H]⁺

(127)1-{2-[2-(1-aminocarbonyl-ethoxy)-phenyl]-2-oxo-ethyl}-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=522 [M+H]⁺

(128)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=435 [M+H]⁺

(129)1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

Melting point: 155-156.5° C.

Mass spectrum (ESI⁺): m/z=472 [M+H]⁺

(130)1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.52 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=472 [M+H]⁺

(131)1-[(4-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.46 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=472 [M+H]⁺

(132)1-[(4-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.46 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=472 [M+H]⁺

(133)1-[(4-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-((E)-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.48 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=474 [M+H]⁺

(134)1-[(4-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-((E)-2-buten-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

Melting point: 167.5-172° C.

Mass spectrum (ESI⁺): m/z=474 [M+H]⁺

(135)1-[2-(2,3-dihydro-benzo[1,4]dioxin-5-yl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.34 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=493 [M+H]⁺

(136)1-[2-(2,3-dihydro-benzo[1,4]dioxin-5-yl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(S)-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

Mass spectrum (ESI⁺): m/z=493 [M+H]⁺

(137)1-[(4-methoxy-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.52 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=487 [M+H]⁺

(138)1-[(4-methoxy-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.52 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=487 [M+H]⁺

(139)1-[2-(benzo[1,3]dioxol-4-yl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.41 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=479 [M+H]⁺

(140)1-[2-(benzo[1,3]dioxol-4-yl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

Mass spectrum (ESI⁺): m/z=479 [M+H]⁺

(141)1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(S)-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.51 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=473 [M+H]⁺

(142)1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

Melting point: 198-202° C.

Mass spectrum (ESI⁺): m/z=473 [M+H]⁺

(143)1-[2-(3-methyl-2-oxo-2,3-dihydro-benzooxazol-4-yl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.53 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=522 [M+H]⁺

(144)1-(2-{2-[(ethylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=538 [M+H]⁺

(145)1-(2-{2-[(isopropylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.49 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:0.1)

Mass spectrum (ESI⁺): m/z=522 [M+H]⁺

(146)1-(2-{2-[(ethylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=508 [M+H]⁺

(147)1-[2-(2-acetylamino-phenyl)-2-oxo-ethyl]-3-methyl-7-((E)-2-buten-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=494 [M+H]⁺

(148)1-(2-{2-[(methylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=524 [M+H]⁺

(149)1-[2-(2-acetylamino-phenyl)-2-oxo-ethyl]-3-methyl-7-((E)-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.49 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:0.1)

Mass spectrum (ESI⁺): m/z=494 [M+H]⁺

(150)1-(2-{2-[(methylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=524 [M+H]⁺

(151)1-(2-{2-[(isopropylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=520 [M+H]⁺

(152)1-(2-{2-[(isopropylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=522 [M+H]⁺

(153)1-(2-{2-[2-(morpholin-4-yl)-2-oxo-ethoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=578 [M+H]⁺

(154)1-(2-{2-[(ethylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.50 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:0.1)

Mass spectrum (ESI⁺): m/z=508 [M+H]⁺

(155)1-(2-{2-[(ethylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=506 [M+H]⁺

(156)1-(2-{2-[(ethylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.20 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=506 [M+H]⁺

(157)1-[2-(2-acetylamino-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=492 [M+H]⁺

(158)1-[2-(2-nitro-3-methoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.49 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=526 [M+H]⁺

(159)1-(2-{2-[(phenylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.49 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:0.1)

Mass spectrum (ESI⁺): m/z=556 [M+H]⁺

(160)1-[(2-acetyl-benzofuran-3-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Obtained as main product when1-{2-[2-(2-oxo-propoxy)-phenyl]-2-oxo-ethyl}-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthineis treated with trifluoroacetic acid in methylene chloride)

Mass spectrum (ESI⁺): m/z=489 [M+H]⁺

(161)1-{2-[2-(1-ethoxycarbonyl-1-methyl-ethoxy)-phenyl]-2-oxo-ethyl}-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=565 [M+H]⁺

(162)1-[2-(2-amino-3-methoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.38 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=496 [M+H]⁺

(163)1-[(4-dimethylamino-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.30 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:0.1)

Mass spectrum (ESI⁺): m/z=502 [M+H]⁺

(164)1-[2-(2-oxo-2,3-dihydro-benzooxazol-7-yl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.42 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=508 [M+H]⁺

(165)1-(2-{2-[(ethoxycarbonyl)methylamino]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.51 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:0.1)

Mass spectrum (ESI⁺): m/z=538 [M+H]⁺

(166)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-((Z)-2-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.29 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=451 [M+H]⁺

(167)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-((E)-2-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.59 (silica gel, methylene chloride/methanol/conc. aqueousammonia=80:20:1)

Mass spectrum (ESI⁺): m/z=451 [M+H]⁺

(168)1-[(imidazo[1,2-a]pyridin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.47 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=447 [M+H]⁺

(169)1-[(quinoxalin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.50 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=459 [M+H]⁺

(170)1-[2-(1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzoimidazol-4-yl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.55 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=519 [M+H]⁺

(171)1-[(quinoxalin-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

Mass spectrum (ESI⁺): m/z=459 [M+H]⁺

(172)1-[(2-cyano-benzofuran-3-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=472 [M+H]⁺

(173)1-[2-(2-oxo-2,3-dihydro-benzooxazol-4-yl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=492 [M+H]⁺

R_(f) value: 0.47 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

(174)1-[(3-methyl-quinoxalin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

Melting point: 188.5-191° C.

Mass spectrum (ESI⁺): m/z=473 [M+H]⁺

(175)1-[(3-phenyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.45 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:1)

Mass spectrum (ESI⁺): m/z=534 [M+H]⁺

(176)1-(2-{2-[(methanesulphinyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthinex trifluoroacetic acid

Mass spectrum (ESI⁺): m/z=527 [M+H]⁺

(177)1-[(benzofuran-3-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Produced when1-{[2-(tert.-butylcarbonyl)-benzofuran-3-yl]methyl}-3-methyl-7-(2-butyn-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthineis treated with trifluoroacetic acid in methylene chloride)

Mass spectrum (ESI⁺): m/z=447 [M+H]⁺

(178)1-[(3,4-dimethyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine-hydrochloride

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.75 (aluminium oxide, methylene chloride/methanol=10:1)

Mass spectrum (ESI⁺): m/z=486 [M+H]⁺

(179)1-[(benzofuran-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=447 [M+H]⁺

(180)1-{[4-(morpholin-4-yl)-quinazolin-2-yl]methyl}-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.45 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:0.1)

Mass spectrum (ESI⁺): m/z=544 [M+H]⁺

(181)1-{[4-(piperidin-1-yl)-quinazolin-2-yl]methyl}-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.55 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:0.1)

Mass spectrum (ESI⁺): m/z=542 [M+H]⁺

(182)1-{[4-(piperazin-1-yl)-quinazolin-2-yl]methyl}-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.23 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:0.1)

Mass spectrum (ESI⁺): m/z=543 [M+H]⁺

(183)1-{[4-(pyrrolidin-1-yl)-quinazolin-2-yl]methyl}-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.50 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:0.1)

Mass spectrum (ESI⁺): m/z=528 [M+H]⁺

(184)1-[2-(3-methyl-2-oxo-2,3-dihydro-1H-benzoimidazol-4-yl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.43 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=505 [M+H]⁺

(185)1-[(4-cyano-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.27 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=482 [M+H]⁺

(186)1-[(imidazo[1,2-a]pyridine-3-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.37 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=447 [M+H]⁺

(187)1-[(8-methyl-imidazo[1,2-a]pyridin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.46 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=461 [M+H]⁺

(188)1-[(4-amino-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.40 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:0.1)

Mass spectrum (ESI⁺): m/z=474 [M+H]⁺

(189)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-((Z)-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=437 [M+H]⁺

(190)1-[(8-methoxy-quinolin-5-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthinex 2 trifluoroacetic acid

R_(f) value: 0.45 (silica gel, methylene chloride/methanol=5:1)

Mass spectrum (ESI⁺): m/z=488 [M+H]⁺

(191)1-[(5-methoxy-quinolin-8-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthinex trifluoroacetic acid

R_(f) value: 0.20 (silica gel, ethyl acetate/methanol=1:1)

Mass spectrum (ESI⁺): m/z=488 [M+H]⁺

(192)1-[(4-phenyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.60 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=535 [M+H]⁺

(193)1-[(7-methyl-imidazo[1,2-a]pyridin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.48 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=461 [M+H]⁺

(194)1-[(2-cyclopropyl-quinazolin-4-yl)methyl]-3-methyl-7-[(1-cyclopenten-1-yl)methyl]-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.55 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:1)

Mass spectrum (ESI⁺): m/z=527 [M+H]⁺

(195)1-(2-oxo-4-phenyl-butyl)-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthinex trifluoroacetic acid

Mass spectrum (ESI⁺): m/z=463 [M+H]⁺

(196)1-(2-{2-[(methylaminocarbonyl)methylamino]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.52 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:0.1)

Mass spectrum (ESI⁺): m/z=523 [M+H]⁺

(197)1-[2-(2-oxo-2,3-dihydro-1H-benzoimidazol-4-yl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.40 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=491 [M+H]⁺

(198)1-[(3-difluoromethyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthinex trifluoroacetic acid

R_(f) value: 0.75 (silica gel, methylene chloride/methanol=10:1)

Mass spectrum (ESI⁺): m/z=508 [M+H]⁺

(199)1-[2-(2,2-difluoro-benzo[1,3]dioxol-4-yl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.80 (silica gel, methylene chloride/methanol/conc. aqueousammonia=96:4:0.5)

Mass spectrum (ESI⁺): m/z=515 [M+H]⁺

(200)1-[(3-methyl-imidazo[1,2-a]pyridin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f)-Wet: 0.45 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=461 [M+H]⁺

(201)1-[2-(2,2-difluoro-benzo[1,3]dioxol-4-yl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

Mass spectrum (ESI⁺): m/z=515 [M+H]⁺

(202)1-[(5-methyl-imidazo[1,2-a]pyridin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.53 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=461 [M+H]⁺

(203)1-[(6-methyl-imidazo[1,2-a]pyridin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

Melting point: 176.5-178° C.

Mass spectrum (ESI⁺): m/z=461 [M+H]⁺

(204)1-[(3-benzyl-imidazo[1,2-a]pyridin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

Melting point: 201-204° C.

Mass spectrum (ESI⁺): m/z=537 [M+H]⁺

(205)1-[(4-isopropyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.50 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:0.1)

Mass spectrum (ESI⁺): m/z=501 [M+H]⁺

(206)1-[(2,3-dihydro-benzo[1,4]dioxin-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.65 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=465 [M+H]⁺

(207)1-[(1-methyl-1H-indol-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine-hydrochloride

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.60 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=460 [M+H]⁺

(208)1-[(quinolin-3-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.50 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:0.1)

Mass spectrum (ESI⁺): m/z=458 [M+H]⁺

(209)1-[(3-phenyl-imidazo[1,2-a]pyridin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.50 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=523 [M+H]⁺

(210)1-[(1H-indol-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine-hydrochloride

R_(f) value: 0.55 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=446 [M+H]⁺

(211)1-[2-(naphthalen-1-yl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.60 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=485 [M+H]⁺

(212)1-[(5-methoxy-isoquinolin-8-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthinex trifluoroacetic acid

R_(f) value: 0.50 (silica gel, methylene chloride/methanol=5:1)

Mass spectrum (ESI⁺): m/z=488 [M+H]⁺

(213)1-{[1-(1-cyano-1-methyl-ethyl)-isoquinolin-3-yl]methyl}-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.25 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:1)

Mass spectrum (ESI⁺): m/z=525 [M+H]⁺

(214)1-(2-cyanoimino-2-phenyl-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthinex trifluoroacetic acid (E/Z-mixture)

Mass spectrum (ESI⁺): m/z=459 [M+H]⁺

(215)1-[(1H-benzoimidazol-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthinex trifluoroacetic acid

Mass spectrum (ESI⁺): m/z=447 [M+H]⁺

(216)1-[(1-methyl-1H-benzoimidazol-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=461 [M+H]⁺

(217)1-[(4-phenyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

Mass spectrum (ESI⁺): m/z=535 [M+H]⁺

(218)1-[(2,3-dimethyl-quinoxalin-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.50 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:0.1)

Mass spectrum (ESI⁺): m/z=487 [M+H]⁺

(219)1-[(2-methyl-1H-benzoimidazol-5-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.35 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:0.1)

Mass spectrum (ESI⁺): m/z=461 [M+H]⁺

(220)1-[(4-phenyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

Mass spectrum (ESI⁺): m/z=535 [M+H]⁺

(221)1-[2-(quinolin-8-yl-]-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.48 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=486 [M+H]⁺

(222)1-[(3,4-dimethyl-6,7-dihydro-5H-[2]pyridin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthinex trifluoroacetic acid

R_(f) value: 0.25 (aluminium oxide, methylene chloride/methanol=20:1)

Mass spectrum (ESI⁺): m/z=476 [M+H]⁺

(223)1-[(3,4-dimethyl-5,6,7,8-tetrahydro-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthinex trifluoroacetic acid

R_(f) value: 0.50 (aluminium oxide, methylene chloride/methanol=20:1)

Mass spectrum (ESI⁺): m/z=490 [M+H]⁺

(224)1-[2-(1H-indol-4-yl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.52 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=474 [M+H]⁺

(225)1-[(1H-benzoimidazol-5-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.50 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=447 [M+H]⁺

(226)1-[(pyrazolo[1,5-a]pyridin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.47 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=447 [M+H]⁺

(227)1-[(1-methyl-2-oxo-1,2-dihydro-quinolin-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.40 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=488 [M+H]⁺

(228)1-[(2-oxo-1,2-dihydro-quinolin-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.23 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=474 [M+H]⁺

(229)1-[(2,3,8-trimethyl-quinoxalin-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.37 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=501 [M+H]⁺

(230)1-[(8-methyl-quinoxalin-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.35 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=473 [M+H]⁺

(231)1-[(4-methyl-phthalazin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.55 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:1)

Mass spectrum (ESI⁺): m/z=473 [M+H]⁺

(232)1-[(4-bromo-3-methoxy-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.40 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:1)

Mass spectrum (ESI⁺): m/z=566, 568 [M+H]⁺

(233)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-((E)-1-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.31 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=437 [M+H]⁺

(234)1-[(4-difluoromethoxy-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.08 (silica gel, methylene chloride/methanol/conc. aqueousammonia=95:5:1)

Mass spectrum (ESI⁺): m/z=523 [M+H]⁺

(235)1-[2-(1H-indol-7-yl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthinex trifluoroacetic acid

R_(f) value: 0.46 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=474 [M+H]⁺

(236)1-[(E)-3-(2-nitro-phenyl)-2-propen-1-yl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=478 [M+H]⁺

(237)1-((E)-3-pentafluorophenyl-2-propen-1-yl)-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=523 [M+H]⁺

(238)1-[(4-nitro-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.38 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=502 [M+H]⁺

(239)1-{[1-(2-cyano-ethyl)-1H-benzoimidazol-2-yl]methyl}-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine-hydrochloride

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.55 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:0.1)

Mass spectrum (ESI⁺): m/z=500 [M+H]⁺

(240)1-({1-[(methylaminocarbonyl)methyl]-1H-benzoimidazol-2-yl}methyl)-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthinex trifluoroacetic acid

Mass spectrum (ESI⁺): m/z=518 [M+H]⁺

(241)1-[(1-benzyl-1H-benzoimidazol-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.47 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:0.1)

Mass spectrum (ESI⁺): m/z=537 [M+H]⁺

(242)1-[(benzooxazol-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthinex trifluoroacetic acid

R_(f) value: 0.50 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:0.1)

Mass spectrum (ESI⁺): m/z=448 [M+H]⁺

(243)1-[(5-nitro-benzooxazol-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.49 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:0.1)

Mass spectrum (ESI⁺): m/z=493 [M+H]⁺

(244)1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(3-methyl-1-buten-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.21 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=488 [M+H]⁺

(245)1-[(quinolin-7-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.55 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=458 [M+H]⁺

(246)1-[([1,5]naphthyridin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.51 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=459 [M+H]⁺

(247)1-[(8-methyl-quinoxalin-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.49 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=473 [M+H]⁺

(248)1-[(2,3,8-trimethyl-quinoxalin-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.46 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=501 [M+H]⁺

(249)1-[([1,6]naphthyridin-5-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.50 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=459 [M+H]⁺

(250)1-[([1,8]naphthyridin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.45 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=459 [M+H]⁺

(251)1-[(4-fluoro-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.50 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=475 [M+H]⁺

(252)1-[([1,5]naphthyridin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

Mass spectrum (ESI⁺): m/z=459 [M+H]⁺

(253)1-[2-(3-methyl-2-oxo-2,3-dihydro-benzooxazol-4-yl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

Melting point: 187-189° C.

Mass spectrum (ESI⁺): m/z=506 [M+H]⁺

(254)1-[(8-phenyl-quinoxalin-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.50 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=535 [M+H]⁺

(255)1-[([1,5]naphthyridine-4-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.52 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=459 [M+H]⁺

(256)1-((E)-3-pentafluorophenyl-allyl)-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=523 [M+H]⁺

(257)1-[(E)-3-(2-trifluoromethyl-phenyl)-allyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=501 [M+H]⁺

(258)1-[(E)-3-(3-trifluoromethyl-phenyl)-allyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=501 [M+H]⁺

(259)1-[(E)-3-(4-trifluoromethyl-phenyl)-allyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=501 [M+H]⁺

(260)1-[(3-trifluoromethyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthinex trifluoroacetic acid

Mass spectrum (ESI⁺): m/z=526 [M+H]⁺

(261)1-[(3-methyl-isoquinolin-1-yl)methyl]-3-isopropyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine(262)1-[(3-methyl-isoquinolin-1-yl)methyl]-3-(4-fluorophenyl)-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine(263)1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-cyano-benzyl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.51 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:1)

Mass spectrum (ESI⁺): m/z=535 [M+H]⁺

(264)1-[(3-difluoromethyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=508 [M+H]⁺

(265)1-[(4-chloro-3-methoxy-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

Mass spectrum (ESI⁺): m/z=522, 524 [M+H]⁺

R_(f) value: 0.40 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:1)

(266)1-[(4-ethoxy-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 1 M ethereal hydrochloric acid)

R_(f) value: 0.60 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:1)

Mass spectrum (ESI⁺): m/z=503 [M+H]⁺

(267)1-[(4-isopropyloxy-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.55 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:1)

Mass spectrum (ESI⁺): m/z=517 [M+H]⁺

(268)1-[(2-methyl-benzothiazol-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

Melting point: 167° C.

Mass spectrum (ESI⁺): m/z=478 [M+H]⁺

(269)1-[(3-phenyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.45 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:1)

Mass spectrum (ESI⁺): m/z=534 [M+H]⁺

(270)1-[(4-phenyloxy-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.60 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:1)

Mass spectrum (ESI⁺): m/z=551 [M+H]⁺

(271)1-[(4-phenyl-quinazolin-2-yl)methyl]-3-cyclopropyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.45 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:1)

Mass spectrum (ESI⁺): m/z=561 [M+H]⁺

(272)1-[(3-methyl-isoquinolin-1-yl)methyl]-3-cyclopropyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.55 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:1)

Mass spectrum (ESI⁺): m/z=498 [M+H]⁺

(273)1-[(2-phenyl-quinazolin-4-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.50 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:1)

Mass spectrum (ESI⁺): m/z=535 [M+H]⁺

(274)1-[2-(2-methoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.29 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=465 [M+H]⁺

(275)1-[2-(3-methoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.27 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=465 [M+H]⁺

(276)1-[2-(3-trifluoromethoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.29 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=519 [M+H]⁺

(277)1-[2-(biphenyl-2-yl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.35 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:1)

Mass spectrum (ESI⁺): m/z=511 [M+H]⁺

(278)1-[2-(biphenyl-3-yl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.35 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:1)

Mass spectrum (ESI⁺): m/z=511 [M+H]⁺

(279)1-[2-(3-isopropyloxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.20 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=493 [M+H]⁺

(280)1-[(3-methyl-isoquinolin-1-yl)methyl]-3-cyclopropyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.50 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:1)

Mass spectrum (ESI⁺): m/z=498 [M+H]⁺

(281)1-[(4-phenyl-quinazolin-2-yl)methyl]-3-cyclopropyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.45 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:1)

Mass spectrum (ESI⁺): m/z=561 [M+H]⁺

(282)1-[(4-cyano-naphthalen-1-yl)methyl]-3-cyclopropyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

Melting point: 191° C.

Mass spectrum (ESI⁺): m/z=508 [M+H]⁺

(283)1-[2-(2-phenyloxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.40 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:1)

Mass spectrum (ESI⁺): m/z=527 [M+H]⁺

(284)1-[2-(3-ethoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.29 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=479 [M+H]⁺

(285)1-[2-(3-methoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.28 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=465 [M+H]⁺

(286)1-[2-(2-methoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.34 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=465 [M+H]⁺

(287)1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-chloro-benzyl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=544, 546 [M+H]⁺

(288)1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-bromo-benzyl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

Mass spectrum (ESI⁺): m/z=588, 590 [M+H]⁺

(289)1-[(1,2,3,4-tetrahydro-phenanthridin-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthinex trifluoroacetic acid

R_(f) value: 0.75 (aluminium oxide, methylene chloride/methanol=10:1)

Mass spectrum (ESI⁺): m/z=512 [M+H]⁺

(290)1-[2-(3-difluoromethoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

(Carried out with 5-6 M isopropanolic hydrochloric acid in methylenechloride)

R_(f) value: 0.28 (silica gel, methylene chloride/methanol/conc. aqueousammonia=90:10:1)

Mass spectrum (ESI⁺): m/z=501 [M+H]⁺

(291)1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-ethynyl-benzyl)-8-((R)-3-amino-piperidin-1-yl)-xanthine(292)1-[(3-methyl-isoquinolin-1-yl)methyl]-3-phenyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine(293)1-[(phenanthren-9-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine(294)1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-chloro-benzyl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.35 (silica gel, methylenechloride/methanol/triethylamine=90:10:1)

Mass spectrum (ESI⁺): m/z=545, 547 [M+H]⁺

(295)1-[(4-phenyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-chloro-benzyl)-8-((R)-3-amino-piperidin-1-yl)-xanthine

R_(f) value: 0.40 (silica gel, methylenechloride/methanol/triethylamine=90:10:1)

Mass spectrum (ESI⁺): m/z=607, 609 [M+H]⁺

EXAMPLE 31-[2-(3-carboxymethoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

Prepared by saponifying 70 mg of1-(2-{3-[(methoxycarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthinewith 0.10 ml of 4 M potassium hydroxide solution in a mixture of 1 ml oftetrahydrofuran and 0.5 ml of methanol at ambient temperature.

Yield: 57 mg (84% of theory)

R_(f) value: 0.55 (ready-made reversed phase TLC plate (E. Merck),acetonitrile/water/trifluoroacetic acid=50:50:0.1)

Mass spectrum (ESI⁺): m/z=525 [M+H]⁺

The following compounds are obtained analogously to Example 3:

(1)1-[2-(2-carboxymethoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(3-methyl-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine

(Carried out with sodium hydroxide solution)

Mass spectrum (ESI⁻): m/z=523 [M−H]⁻

EXAMPLE 4

Coated tablets containing 75 mg of active substance 1 tablet corecontains: active substance 75.0 mg calcium phosphate 93.0 mg corn starch35.5 mg polyvinylpyrrolidone 10.0 mg hydroxypropylmethylcellulose 15.0mg magnesium stearate  1.5 mg 230.0 mg 

Preparation:

The active substance is mixed with calcium phosphate, corn starch,polyvinylpyrrolidone, hydroxypropylmethylcellulose and half thespecified amount of magnesium stearate. Blanks 13 mm in diameter areproduced in a tablet-making machine and these are then rubbed through ascreen with a mesh size of 1.5 mm using a suitable machine and mixedwith the rest of the magnesium stearate. This granulate is compressed ina tablet-making machine to form tablets of the desired shape.

Weight of core: 230 mg die:  9 mm, convex

The tablet cores thus produced are coated with a film consistingessentially of hydroxypropylmethylcellulose. The finished film-coatedtablets are polished with beeswax.

-   -   Weight of coated tablet: 245 mg.

EXAMPLE 5

Tablets containing 100 mg of active substance Composition: 1 tabletcontains: active substance 100.0 mg lactose 80.0 mg corn starch 34.0 mgpolyvinylpyrrolidone 4.0 mg magnesium stearate 2.0 mg 220.0 mg

Method of Preparation:

The active substance, lactose and starch are mixed together anduniformly moistened with an aqueous solution of thepolyvinylpyrrolidone. After the moist composition has been screened (2.0mm mesh size) and dried in a rack-type drier at 50° C. it is screenedagain (1.5 mm mesh size) and the lubricant is added. The finishedmixture is compressed to form tablets.

-   -   Weight of tablet: 220 mg    -   Diameter: 10 mm, biplanar, facetted on both sides and notched on        one side.

EXAMPLE 6

Tablets containing 150 mg of active substance Composition: 1 tabletcontains: active substance 150.0 mg powdered lactose 89.0 mg corn starch40.0 mg colloidal silica 10.0 mg polyvinylpyrrolidone 10.0 mg magnesiumstearate 1.0 mg 300.0 mg

Preparation:

The active substance mixed with lactose, corn starch and silica ismoistened with a 20% aqueous polyvinylpyrrolidone solution and passedthrough a screen with a mesh size of 1.5 mm. The granules, dried at 45°C., are passed through the same screen again and mixed with thespecified amount of magnesium stearate. Tablets are pressed from themixture.

-   -   Weight of tablet: 300 mg    -   die: 10 mm, flat

EXAMPLE 7

Hard gelatine capsules containing 150 mg of active substance 1 capsulecontains: active substance 150.0 mg corn starch (dried approx. 80.0 mglactose (powdered) approx. 87.0 mg magnesium stearate 3.0 mg approx.420.0 mg

Preparation:

The active substance is mixed with the excipients, passed through ascreen with a mesh size of 0.75 mm and homogeneously mixed using asuitable apparatus. The finished mixture is packed into size 1 hardgelatine capsules.

-   -   Capsule filling: approx. 320 mg    -   Capsule shell: size 1 hard gelatine capsule.

EXAMPLE 8

Suppositories containing 150 mg of active substance 1 suppositorycontains: active substance 150.0 mg polyethyleneglycol 1500 550.0 mgpolyethyleneglycol 6000 460.0 mg polyoxyethylene sorbitan monostearate840.0 mg 2,000.0 mg  

Preparation:

After the suppository mass has been melted the active substance ishomogeneously distributed therein and the melt is poured into chilledmoulds.

EXAMPLE 9

Suspension containing 50 mg of active substance 100 ml of suspensioncontain: active substance 1.00 g carboxymethylcellulose-Na-salt 0.10 gmethyl p-hydroxybenzoate 0.05 g propyl p-hydroxybenzoate 0.01 g glucose10.00 g glycerol 5.00 g 70% sorbitol solution 20.00 g flavouring 0.30 gdist. water ad 100 ml

Preparation:

The distilled water is heated to 70° C. The methyl and propylp-hydroxybenzoates together with the glycerol and sodium salt ofcarboxymethylcellulose are dissolved therein with stirring. The solutionis cooled to ambient temperature and the active substance is added andhomogeneously dispersed therein with stirring. After the sugar, thesorbitol solution and the flavouring have been added and dissolved, thesuspension is evacuated with stirring to eliminate air.

-   -   5 ml of suspension contain 50 mg of active substance.

EXAMPLE 10

Ampoules containing 10 mg active substance Composition: active substance10.0 mg 0.01 N hydrochloric acid q.s. double-distilled water ad 2.0 ml

Preparation:

The active substance is dissolved in the necessary amount of 0.01 N HCl,made isotonic with common salt, filtered sterile and transferred into 2ml ampoules.

EXAMPLE 11

Ampoules containing 50 mg of active substance Composition: activesubstance 50.0 mg 0.01 N hydrochloric acid q.s. double-distilled waterad 10.0 ml

Preparation:

The active substance is dissolved in the necessary amount of 0.01 N HCl,made isotonic with common salt, filtered sterile and transferred into 10ml ampoules.

1.-22. (canceled)
 23. A pharmaceutical composition comprising: a firstcompound of the formula (I):

wherein R¹ denotes: a methyl group which is substituted by adimethylaminocarbonyl, pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl,tert.-butylcarbonyl or a cyclohexylcarbonyl group, a methyl group whichis substituted by a naphthyl, methylnaphthyl, methoxynaphthyl,nitronaphthyl or (dimethylamino)-naphthyl group, a methyl group which issubstituted by a 2-phenylethenyl or a biphenylyl group, a methyl groupwhich is substituted by a phenyl-oxadiazolyl,5-methyl-3-phenyl-isoxazolyl, phenyl-pyridinyl, indolyl,benzothiophenyl, quinolinyl, isoquinolinyl, methylisoquinolinyl,(methoxycarbonylmethylamino)-isoquinolinyl, cinnolinyl, quinazolinyl,methylquinazolinyl, 1,2-dihydro-1-methyl-2-oxo-quinolinyl,1,2-dihydro-2-methyl-1-oxo-isoquinolinyl,3,4-dihydro-4-oxo-phthalazinyl, 3,4-dihydro-3-methyl-4-oxo-phthalazinyl,3,4-dihydro-4-oxo-quinazolinyl, 3,4-dihydro-3-methyl-4-oxo-quinazolinylor a 2-oxo-2H-chromenyl group, a 2-methoxyethyl, 2-phenyloxyethyl or2-cyanoethyl group, a phenylcarbonylmethyl or a 1-(phenylcarbonyl)-ethylgroup, a phenylcarbonylmethyl group wherein the phenyl moiety issubstituted by an amino, cyanomethylamino, methylcarbonylamino,ethylcarbonylamino, isopropylcarbonylamino, methoxycarbonylamino,(ethyloxycarbonylamino)-carbonylamino or a 2-oxo-imidazolidin-1-ylgroup, a phenylcarbonylmethyl group wherein the phenyl moiety issubstituted by a carboxy, methoxycarbonyl, ethyloxycarbonyl,aminocarbonyl, methylaminocarbonyl, dimethyl-aminocarbonyl ormorpholin-4-ylcarbonyl group, a phenylcarbonylmethyl group wherein thephenyl moiety is substituted by a methylsulphanyl, methylsulphinyl ormethylsulphonyl group, a phenylcarbonylmethyl group wherein the phenylmoiety is substituted by a carboxymethoxy, ethyloxycarbonylmethoxy,isopropyloxycarbonylmethoxy, aminocarbonylmethoxy,methylaminocarbonylmethoxy, ethylaminocarbonylmethoxy,isopropylaminocarbonylmethoxy, dimethylaminocarbonylmethoxy,pyrrolidin-1-ylcarbonylmethoxy or morpholin-4-ylcarbonylmethoxy group, aphenylcarbonylmethyl group wherein the phenyl moiety is substituted by a1-(methoxy-carbonyl)-ethyloxy or a 1-(aminocarbonyl)-ethyloxy group, aphenylcarbonylmethyl group wherein the phenyl moiety is substituted by amethylsulphinyl-methoxy group, a phenylcarbonylmethyl group wherein thephenyl moiety is substituted by two methoxy groups, or aphenylcarbonylmethyl group wherein in the phenyl moiety two adjacenthydrogen atoms are replaced by a —O—CH₂—O, —O—CH₂—CH₂—O or a—N(CH₃)—CO—O group; R² denotes a methyl, isopropyl or phenyl group; andR³ denotes: a 2-methyl-2-propen-1-yl, 2-chloro-2-propen-1-yl or3-bromo-2-propen-1-yl group a 2-buten-1-yl or 2,3-dimethyl-2-buten-1-ylgroup, a 2-butyn-1-yl group, a 1-cyclopenten-1-ylmethyl group or a2-furanylmethyl group; or a tautomer, enantiomer, diastereomer, mixturethereof, a prodrug thereof or a salt thereof; and one or more othertherapeutic agents selected from antidiabetics, lipid lowering agents,active substances for the treatment of obesity, and drugs for treatinghigh blood pressure; optionally together with one or more inert carriersand/or diluents.
 24. The pharmaceutical composition of claim 23, whereinsaid composition comprises at least one antidiabetic selected from thegroup consisting of: metformin, a sulphonylurea, nateglinide,repaglinide, a thiazolidinedione, a PPAR-gamma agonist or antagonist, aPPAR-gamma/alpha modulator, an alpha-glucosidase inhibitor, anotherDPPIV inhibitor, an alpha2 antagonist, insulin or an insulin analogue,GLP-1 or a GLP-1 analogue, amylin, an SGLT2 inhibitor, an inhibitor ofprotein tyrosine phosphatase 1, an inhibitor of glucose-6-phosphatase,an inhibitor of fructose-1,6-bisphosphatase, an inhibitor of glycogenphosphorylase, a glucagon receptor antagonist, an inhibitor ofphosphoenolpyruvate carboxykinase, an inhibitor of glycogen synthasekinase, and an inhibitor of pyruvate dehydrokinase.
 25. Thepharmaceutical composition of claim 24, wherein said compositioncomprises at least one antidiabetic sulphonylurea selected fromglibenclamide, tolbutamide and glimepriride.
 26. The pharmaceuticalcomposition of claim 24, wherein said composition comprises at least oneantidiabetic thiazolidinedione selected from rosiglitazone andpioglitazone.
 27. The pharmaceutical composition of claim 24, whereinsaid composition comprises at least one antidiabetic alpha-glucosidaseinhibitor selected from acarbose and voglibose.
 28. The pharmaceuticalcomposition of claim 23, wherein said composition comprises at least onelipid lowering agent selected from the group consisting of: anHMG-CoA-reductase inhibitor, a fibrate, nicotinic acid, a nictonic acidderivative, a PPAR-alpha agonist, a PPAR-delta agonists, an ACATinhibitor, a cholesterol resorption inhibitor, a bile acid-bindingsubstance, an inhibitor of ileac bile acid transport, an HDL-raisingcompound, an inhibitor of CETP, and a regulator of ABC1.
 29. Thepharmaceutical composition of claim 28, wherein said compositioncomprises at least one HMG-CoA-reductase inhibitor selected fromsimvastatin and atorvastatin.
 30. The pharmaceutical composition ofclaim 28, wherein said composition comprises at least one fibrateselected from bezafibrate and fenofibrate.
 31. The pharmaceuticalcomposition of claim 28, wherein said composition comprises at least onecholesterol resorption inhibitor which is ezetimibe.
 32. Thepharmaceutical composition of claim 23, wherein said compositioncomprises at least one active substance for the treatment of obesityselected from the group consisting of: sibutramine,tetrahydrolipostatin, dexfenfluramine, axokine, an antagonist of thecannabinoid1 receptor, a MCH-1 receptor antagonist, a MC4 receptoragonist, a NPY5 or NPY2 antagonist, a β₃-agonist, and an agonist of the5HT2c receptor.
 33. The pharmaceutical composition of claim 23, whereinsaid composition comprises at least one drug for treating high bloodpressure selected from the group consisting of: an AII antagonist, anACE inhibitor, a diuretic, a β-blocker, and a Ca-antagonist.
 34. Thepharmaceutical composition of claim 23, wherein said first compound isof formula (I) wherein: R¹ denotes: a 4-methoxy-1-naphthylmethyl group,a 2-quinolinylmethyl, 4-quinolinylmethyl or a 6-quinolinylmethyl group,a 1-isoquinolinylmethyl, 3-methyl-1-isoquinolinylmethyl,4-methyl-1-isoquinolinyl-methyl or a 3-isoquinolinylmethyl group, or a2-quinazolinylmethyl, 4-methyl-2-quinazolinylmethyl or a4-quinazolinylmethyl group; R² denotes a methyl group; and R³ denotes a2-buten-1-yl or a 2-butyn-1-yl group; or a tautomer, enantiomer,diastereomer, mixture thereof, or a salt thereof.
 35. The pharmaceuticalcomposition of claim 23, wherein said first compound of the formula (I)is chosen from: (1)1-[(quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(2)1-(2-{2-[(ethylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(3)1-(2-{2-[(methylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(4)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(5)1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,(6)1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(7)1-[(4-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,(8)1-[(4-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(9)1-[2-(2,3-dihydro-benzo[1,4]dioxin-5-yl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine,(10)1-[(4-methoxy-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,(11)1-[(4-methoxy-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(12)1-[2-(benzo[1,3]dioxol-4-yl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(13)1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine,(14)1-(2-{2-[(isopropylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,(15)1-(2-{2-[(methylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(16)1-(2-{2-[(methylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,(17)1-(2-{2-[(isopropylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(18)1-(2-{2-[(isopropylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(19)1-[(4-cyano-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(20)1-[(4-phenyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(21)-[(8-methyl-quinoxalin-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(22)1-[(4-fluoro-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(23)1-((E)-3-pentafluorophenyl-allyl)-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(24)1-[(3-trifluoromethyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(25)1-[(3-difluoromethyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(26)1-[2-(biphenyl-2-yl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(27)1-[(3-methyl-isoquinolin-1-yl)methyl]-3-cyclopropyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(28)1-[2-(3-methoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(29)1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-chloro-benzyl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(30)1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-bromo-benzyl)-8-((R)-3-amino-piperidin-1-yl)-xanthine;or a tautomer, enantiomer, diastereomer, mixture thereof or a saltthereof.
 36. The pharmaceutical composition of claim 23, wherein saidfirst compound of the formula (I) is chosen from:1-[(4-methoxy-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-3-amino-piperidin-1-yl)-xanthine,1-[(4-methoxy-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,1-[(4-methoxy-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,1-[(quinolin-4-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,1-[(quinolin-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,1-[(isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,1-[(4-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,1-[(4-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,1-[(4-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,1-[(isoquinolin-1-yl)methyl]-3-methyl-7-((E)-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-((E)-2-buten-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-((E)-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,1-[(4-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-((E)-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,1-[(4-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-((E)-2-buten-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,1-[(quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,1-[(quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,1-[(quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,1-[(quinazolin-2-yl)methyl]-3-methyl-7-((E)-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,1-[(quinazolin-2-yl)methyl]-3-methyl-7-((E)-2-buten-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(S)-amino-piperidin-1-yl)-xanthine,1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine;or a tautomer, enantiomer, diastereomer, mixture thereof or a saltthereof.
 37. The pharmaceutical composition of claim 23, wherein saidfirst compound is a physiologically acceptable salt of a compound offormula I, with an inorganic or organic acid or base.
 38. Thepharmaceutical composition of claim 34, wherein said first compound is aphysiologically acceptable salt of a compound of formula I, with aninorganic or organic acid or base.
 39. The pharmaceutical composition ofclaim 35, wherein said first compound is a physiologically acceptablesalt of a compound of formula I, with an inorganic or organic acid orbase.
 40. The pharmaceutical composition of claim 36, wherein said firstcompound is a physiologically acceptable salt of a compound of formulaI, with an inorganic or organic acid or base.
 41. A method of treatingtype I or type II diabetes mellitus or obesity comprising administeringto a patient in need thereof a pharmaceutically effective amount of afirst compound of the formula (I):

wherein R¹ denotes: a methyl group which is substituted by adimethylaminocarbonyl, pyrrolidin-1-ylcarbonyl, piperidin-1-ylcarbonyl,tert.-butylcarbonyl or a cyclohexylcarbonyl group, a methyl group whichis substituted by a naphthyl, methylnaphthyl, methoxynaphthyl,nitronaphthyl or (dimethylamino)-naphthyl group, a methyl group which issubstituted by a 2-phenylethenyl or a biphenylyl group, a methyl groupwhich is substituted by a phenyl-oxadiazolyl,5-methyl-3-phenyl-isoxazolyl, phenyl-pyridinyl, indolyl,benzothiophenyl, quinolinyl, isoquinolinyl, methylisoquinolinyl,(methoxycarbonylmethylamino)-isoquinolinyl, cinnolinyl, quinazolinyl,methylquinazolinyl, 1,2-dihydro-1-methyl-2-oxo-quinolinyl,1,2-dihydro-2-methyl-1-oxo-isoquinolinyl,3,4-dihydro-4-oxo-phthalazinyl, 3,4-dihydro-3-methyl-4-oxo-phthalazinyl,3,4-dihydro-4-oxo-quinazolinyl, 3,4-dihydro-3-methyl-4-oxo-quinazolinylor a 2-oxo-2H-chromenyl group, a 2-methoxyethyl, 2-phenyloxyethyl or2-cyanoethyl group, a phenylcarbonylmethyl or a 1-(phenylcarbonyl)-ethylgroup, a phenylcarbonylmethyl group wherein the phenyl moiety issubstituted by an amino, cyanomethylamino, methylcarbonylamino,ethylcarbonylamino, isopropylcarbonylamino, methoxycarbonylamino,(ethyloxycarbonylamino)-carbonylamino or a 2-oxo-imidazolidin-1-ylgroup, a phenylcarbonylmethyl group wherein the phenyl moiety issubstituted by a carboxy, methoxycarbonyl, ethyloxycarbonyl,aminocarbonyl, methylaminocarbonyl, dimethyl-aminocarbonyl ormorpholin-4-ylcarbonyl group, a phenylcarbonylmethyl group wherein thephenyl moiety is substituted by a methylsulphanyl, methylsulphinyl ormethylsulphonyl group, a phenylcarbonylmethyl group wherein the phenylmoiety is substituted by a carboxymethoxy, ethyloxycarbonylmethoxy,isopropyloxycarbonylmethoxy, aminocarbonylmethoxy,methylaminocarbonylmethoxy, ethylaminocarbonylmethoxy,isopropylaminocarbonylmethoxy, dimethylaminocarbonylmethoxy,pyrrolidin-1-ylcarbonylmethoxy or morpholin-4-ylcarbonylmethoxy group, aphenylcarbonylmethyl group wherein the phenyl moiety is substituted by a1-(methoxy-carbonyl)-ethyloxy or a 1-(aminocarbonyl)-ethyloxy group, aphenylcarbonylmethyl group wherein the phenyl moiety is substituted by amethylsulphinyl-methoxy group, a phenylcarbonylmethyl group wherein thephenyl moiety is substituted by two methoxy groups, or aphenylcarbonylmethyl group wherein in the phenyl moiety two adjacenthydrogen atoms are replaced by a —O—CH₂—O, —O—CH₂—CH₂—O or a—N(CH₃)—CO—O group; R² denotes a methyl, isopropyl or phenyl group; andR³ denotes: a 2-methyl-2-propen-1-yl, 2-chloro-2-propen-1-yl or3-bromo-2-propen-1-yl group a 2-buten-1-yl or 2,3-dimethyl-2-buten-1-ylgroup, a 2-butyn-1-yl group, a 1-cyclopenten-1-ylmethyl group or a2-furanylmethyl group; or a tautomer, enantiomer, diastereomer, mixturethereof, a prodrug thereof or a salt thereof; and a pharmaceuticallyeffective amount of one or more other therapeutic agents selected fromantidiabetics, lipid lowering agents, active substances for thetreatment of obesity, and drugs for treating high blood pressure. 42.The method of claim 41, wherein said other therapeutic agent comprisesat least one antidiabetic selected from the group consisting of:metformin, a sulphonylurea, nateglinide, repaglinide, athiazolidinedione, a PPAR-gamma agonist or antagonist, aPPAR-gamma/alpha modulator, an alpha-glucosidase inhibitor, anotherDPPIV inhibitor, an alpha2 antagonist, insulin or an insulin analogue,GLP-1 or a GLP-1 analogue, amylin, an SGLT2 inhibitor, an inhibitor ofprotein tyrosine phosphatase 1, an inhibitor of glucose-6-phosphatase,an inhibitor of fructose-1,6-bisphosphatase, an inhibitor of glycogenphosphorylase, a glucagon receptor antagonist, an inhibitor ofphosphoenolpyruvate carboxykinase, an inhibitor of glycogen synthasekinase, and an inhibitor of pyruvate dehydrokinase.
 43. The method ofclaim 42, wherein said other therapeutic agent comprises at least oneantidiabetic sulphonylurea selected from glibenclamide, tolbutamide andglimepriride.
 44. The method of claim 42, wherein said other therapeuticagent comprises at least one antidiabetic thiazolidinedione selectedfrom rosiglitazone and pioglitazone.
 45. The method of claim 42, whereinsaid other therapeutic agent comprises at least one antidiabeticalpha-glucosidase inhibitor selected from acarbose and voglibose. 46.The method of claim 41, wherein said other therapeutic agent comprisesat least one lipid lowering agent selected from the group consisting of:an HMG-CoA-reductase inhibitor, a fibrate, nicotinic acid, a nictonicacid derivative, a PPAR-alpha agonist, a PPAR-delta agonists, an ACATinhibitor, a cholesterol resorption inhibitor, a bile acid-bindingsubstance, an inhibitor of ileac bile acid transport, an HDL-raisingcompound, an inhibitor of CETP, and a regulator of ABC1.
 47. The methodof claim 46, wherein said other therapeutic agent comprises at least oneHMG-CoA-reductase inhibitor selected from simvastatin and atorvastatin.48. The method of claim 46, wherein said other therapeutic agentcomprises at least one fibrate selected from bezafibrate andfenofibrate.
 49. The method of claim 46, wherein said other therapeuticagent comprises at least one cholesterol resorption inhibitor which isezetimibe.
 50. The method of claim 41, wherein said other therapeuticagent comprises at least one active substance for the treatment ofobesity selected from the group consisting of: sibutramine,tetrahydrolipostatin, dexfenfluramine, axokine, an antagonist of thecannabinoid1 receptor, a MCH-1 receptor antagonist, a MC4 receptoragonist, a NPY5 or NPY2 antagonist, a β₃-agonist, and an agonist of the5HT2c receptor.
 51. The method of claim 41, wherein said othertherapeutic agent comprises at least one drug for treating high bloodpressure selected from the group consisting of: an AII antagonist, anACE inhibitor, a diuretic, a β-blocker, and a Ca-antagonist.
 52. Themethod of claim 41, wherein said first compound is of formula (I)wherein: R¹ denotes: a 4-methoxy-1-naphthylmethyl group, a2-quinolinylmethyl, 4-quinolinylmethyl or a 6-quinolinylmethyl group, a1-isoquinolinylmethyl, 3-methyl-1-isoquinolinylmethyl,4-methyl-1-isoquinolinyl-methyl or a 3-isoquinolinylmethyl group, or a2-quinazolinylmethyl, 4-methyl-2-quinazolinylmethyl or a4-quinazolinylmethyl group; R² denotes a methyl group; and R³ denotes a2-buten-1-yl or a 2-butyn-1-yl group; or a tautomer, enantiomer,diastereomer, mixture thereof, or a salt thereof.
 53. The method ofclaim 41, wherein said first compound is a compound of the formula (I)chosen from: (1)1-[(quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(2)1-(2-{2-[(ethylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(3)1-(2-{2-[(methylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(4)1-(2-phenyl-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(5)1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,(6)1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(7)1-[(4-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,(8)1-[(4-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(9)1-[2-(2,3-dihydro-benzo[1,4]dioxin-5-yl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine,(10)1-[(4-methoxy-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,(11)1-[(4-methoxy-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(12)1-[2-(benzo[1,3]dioxol-4-yl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(13)1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine,(14)1-(2-{2-[(isopropylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,(15)1-(2-{2-[(methylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(16)1-(2-{2-[(methylaminocarbonyl)methoxy]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,(17)1-(2-{2-[(isopropylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(18)1-(2-{2-[(isopropylcarbonyl)amino]-phenyl}-2-oxo-ethyl)-3-methyl-7-((E)-2-buten-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(19)1-[(4-cyano-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(20)1-[(4-phenyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(21)1-[(8-methyl-quinoxalin-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(22)1-[(4-fluoro-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(23)1-((E)-3-pentafluorophenyl-allyl)-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(24)1-[(3-trifluoromethyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(25)1-[(3-difluoromethyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(26)1-[2-(biphenyl-2-yl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(27)1-[(3-methyl-isoquinolin-1-yl)methyl]-3-cyclopropyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(28)1-[2-(3-methoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(29)1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-chloro-benzyl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,(30)1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-bromo-benzyl)-8-((R)-3-amino-piperidin-1-yl)-xanthine;or a tautomer, enantiomer, diastereomer, mixture thereof or a saltthereof.
 54. The method of claim 41, wherein said first compound is acompound of the formula (I) chosen from:1-[(4-methoxy-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-3-amino-piperidin-1-yl)-xanthine,1-[(4-methoxy-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,1-[(4-methoxy-naphthalen-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,1-[(quinolin-4-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,1-[(quinolin-6-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,1-[(isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,1-[(4-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,1-[(4-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,1-[(4-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,1-[(isoquinolin-1-yl)methyl]-3-methyl-7-((E)-2-buten-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-((E)-2-buten-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,1-[(3-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-((E)-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,1-[(4-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-((E)-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,1-[(4-methyl-isoquinolin-1-yl)methyl]-3-methyl-7-((E)-2-buten-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,1-[(quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,1-[(quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,1-[(quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-piperidin-1-yl)-xanthine,1-[(quinazolin-2-yl)methyl]-3-methyl-7-((E)-2-buten-1-yl)-8-((S)-3-amino-piperidin-1-yl)-xanthine,1-[(quinazolin-2-yl)methyl]-3-methyl-7-((E)-2-buten-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthine,1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(S)-amino-piperidin-1-yl)-xanthine,1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine,or a tautomer, enantiomer, diastereomer, mixture thereof or a saltthereof.
 55. The method of claim 41, wherein said first compound is aphysiologically acceptable salt of a compound of formula I, with aninorganic or organic acid or base.
 56. The method of claim 41, whereinsaid first compound is a physiologically acceptable salt of a compoundof formula I, with an inorganic or organic acid or base.
 57. The methodof claim 41, wherein said first compound is a physiologically acceptablesalt of a compound of formula I, with an inorganic or organic acid orbase.
 58. The method of claim 41, wherein said first compound is aphysiologically acceptable salt of a compound of formula I, with aninorganic or organic acid or base.